Stephen Tzang - Academia.edu (original) (raw)

Papers by Stephen Tzang

Research paper thumbnail of Augmentation of Thermotolerance in Primary Skin Fibroblasts from a Transgenic Pig Overexpressing the Porcine HSP70.2

Asian-Australasian Journal of Animal Sciences, 2005

A high environmental temperature affects the economic performance of pigs. Heat shock protein 70 ... more A high environmental temperature affects the economic performance of pigs. Heat shock protein 70 (HSP70) has been reported to participate importantly in thermotolerance. This study aims to produce transgenic pigs overexpressing porcine HSP70.2, the highly inducible one of HSP70 members, and to prove the cellular thermotolerance in the primary fibroblasts from the transgenics. A recombinant plasmid in which the sequence that encodes the porcine HSP70.2 gene is fused to green fluorescence protein (GFP) was constructed under the control of cytomegalovirus (CMV) enhancer and promoter. Two transgenic pigs were produced by microinjecting pCMV-HSP70-GFP DNA into the pronucleus of fertilized eggs. Immunoblot assay revealed the varied overexpression level (6.4% and 1.4%) of HSP70-GFP in transgenic pigs. After heating at 45°C for 3 h, the survival rate (78.1%) of the primary fibroblast cells from the highly expressing transgenic pig exceeded that from the non-transgenic pig (62.9%). This result showed that primary fibroblasts overexpressing HSP70-GFP confer cell thermotolerance. We suggest that transgenic pigs overexpressing HSP70 might improve their thermotolerance in summer and therefore reduce the economic loss in animal production.

Research paper thumbnail of Hypolipidemic and Antioxidative Effects of Noni (Morinda citrifolia L.) Juice on High- fat/Cholesterol-Dietary Hamsters

Plant Foods for Human Nutrition, 2012

Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and antioxidative e... more Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and antioxidative effects of NJ were investigated in this study. Fifty male hamsters were assigned randomly to one of the following groups: (1) normal diet and distilled water (LFCD); (2) high-fat/cholesterol diet and distilled water (HFCD); (3) HFCD and 3 ml NJ (including 0.20 g solids)/kg BW (NJ_L); (4) HFCD and 6 mL NJ (including 0.40 g solids)/kg BW (NJ_M); (5) HFCD and 9 ml NJ (including 0.60 g solids)/kg BW (NJ_H) for six weeks. NJ supplementation decreased (p<0.05) serum triacylglycerol, cholesterol, atherogenic index, malondialdehyde levels, and hepatic lipids in HFCD hamsters, whereas serum trolox equivalent antioxidant capacity, glutathione, and fecal lipids in HFCD hamsters were increased (p<0.05) by NJ supplementation. Although NJ supplementation downregulated (p<0.05) sterol regulator element binding protein-1c in HFCD hamsters, it upregulated (p<0.05) hepatic peroxisome proliferatoractivated receptor-alpha and uncoupling protein 2 gene expressions in HFCD hamsters. Results demonstrate that NJ promotes cardioprotection in a high-fat/cholesterol diet.

Research paper thumbnail of Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

PLoS ONE, 2013

Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence... more Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor-a (TNF-a), TNF-a receptor, IkB kinase-a (IKK-a), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IkB) and nuclear factor-kappa B (NF-kB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and Uplasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE.

Research paper thumbnail of Increased cardiac injury in NZB/W F1 mice received antibody against human parvovirus B19 VP1 unique region protein

Molecular Immunology, 2011

Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and developmen... more Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and development of systemic lupus erythematosus (SLE). However, the influence of anti-B19-VP1u antibodies on cardiac disorders in SLE is still obscure. To elucidate the effects of anti-B19-VP1u IgG in SLE, passive transfer of PBS, normal rabbit IgG or rabbit anti-B19-VP1u IgG was injected intravenously into NZB/W F1 mice, respectively. Significant expression of IL-1β, IL-6 and TNF-α were detected in NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Markedly cardiomyocyte disarray and lymphocyte infiltration were observed in left ventricle of hearts from NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Additionally, significant increases of matrix metalloproteinase-9 (MMP9) activity and protein expression were detected in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. Accordingly, significant increase of phosphorylated p-38 and NF-κB proteins were observed in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. However, no significant variation of cardiac atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), heart-type fatty acid-binding protein (h-FABP) and creatine kinase MB (CK-MB) were detected among all experimental groups. These findings firstly demonstrated the aggravated effects of anti-B19 VP1u IgG on cardiac injury by induction of inflammatory but not myocardial infarction-associated proteins through activation of phosphorylated p-38 and NF-κB signaling.

Research paper thumbnail of Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

PLoS ONE, 2014

As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important huma... more As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-a (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-a or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-a, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity.

Research paper thumbnail of Exacerbating Effects of Human Parvovirus B19 NS1 on Liver Fibrosis in NZB/W F1 Mice

PLoS ONE, 2013

Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts v... more Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-b/Smad fibrotic signaling by increasing the expressions of TGF-b, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and a-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.

Research paper thumbnail of Cardiac Fas Receptor-dependent Apoptotic Pathway in Obese Zucker Rats**

Obesity, 2007

Very limited information regarding the cardiac molecular mechanism in obesity is available. The p... more Very limited information regarding the cardiac molecular mechanism in obesity is available. The purpose of this study was to evaluate the cardiac Fas receptor-dependent (type I) apoptotic pathway in obese Zucker rats. Sixteen obese Zucker rats were studied at 5 to 6 months of age, and 16 age-matched lean Zucker rats served as controls. Heart weight index, myocardial architecture, key components of the Fas receptor-dependent apoptotic pathway, apoptotic activity, and fibrosis in the excised left ventricle of rats were measured by weight scales, hematoxylin and eosin staining, Western blotting, TUNEL assay, and Masson trichrome staining. Body weight, whole heart weight, left ventricular weight, ratio of whole heart weight to tibia length, percentage of TUNEL-positive cardiac myocytes, and percentage of cardiac fibrosis were significantly increased in the obese group. Cardiomyocyte disarray and increased cardiac interstitial space were observed in obese rats. Protein levels of Fas ligand, Fas death receptors, and Fas-associated Death Domain were all significantly increased in the obese group. In addition, pro-caspase-8 and pro-caspase-3 were significantly decreased, whereas activated caspase-8 and activated caspase-3 were significantly increased in the obese group, which implies that pro-forms of caspase-8 and caspase-3 were cleaved into active-forms caspase-8 and caspase-3. Cardiac Fas receptor-dependent apoptotic pathways were more activated in obese rats&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; hearts, which may provide one of the possible apoptotic mechanisms for developing cardiac abnormality in obesity.

Research paper thumbnail of More Activated Cardiac Mitochondrial-dependent Apoptotic Pathway in Obese Zucker Rats**

Obesity, 2007

Obesity is often associated with the development of heart failure, but the precise mechanisms rem... more Obesity is often associated with the development of heart failure, but the precise mechanisms remain uncertain. The purpose of this study was to evaluate the key components of the mitochondrial-dependent apoptotic pathway in excised heart from obese Zucker rats. Twelve obese Zucker rats were studied at 5 to 6 months of age, and 12 age-matched lean Zucker rats served as control. The myocardial architecture and key components of the mitochondrial-dependent apoptotic pathway in the excised left ventricle from rats were measured by histopathological analysis, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR). The ratios of whole heart weight to tibia length were significantly increased in the obese group. Cardiomyocyte disarray, the increased interstitial space, and minor cardiac fibrosis were observed in obese rat hearts. Pro-apoptotic Bcl2 family members, Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3) and Bad levels, were significantly increased in obese rat hearts, whereas anti-apoptotic Bcl2 family member, Bcl2 level, was significantly decreased. Cytosolic cytochrome c indicating cytochrome c release from mitochondria was significantly increased in obese rat heart. In addition, upstream pro-caspase-9 and pro-caspase-3 were significantly decreased, whereas activated caspase-9 and activated caspase-3 were significantly increased in obese rat hearts, compared with lean rat heart, implying that pro-forms of caspase-9 and caspase-3 were cleaved into active-forms caspase-9 and caspase-3. The cardiac mitochondrial-dependent apoptotic pathway was more activated in obese Zucker rats than in lean rats, which may provide one possible apoptotic mechanism for developing heart failure in obesity.

Research paper thumbnail of Cystamine ameliorates ventricular hypertrophy associated with modulation of IL-6-mediated signaling in lupus-prone mice

Life Sciences, 2013

The aim of this study is to investigate the protective effects of cystamine on lupus-associated c... more The aim of this study is to investigate the protective effects of cystamine on lupus-associated cardiac hypertrophy. Main methods: Balb/c and lupus-prone NZB/W-F1 mice were individually randomized into sham group (saline, n = 16) and cystamine group (n = 16). Mice received saline or cystamine (100 mmol in 100 μL saline) by daily intraperitoneal injection for 2 consecutive weeks. Morphological, histological, and biochemical alterations were investigated. Key findings: Cystamine decreased both left ventricular (LV) mass and LV mass/tissue-to-blood ratio (TBR) in NZB/W-F1 mice (p b 0.05), whereas slight effects were observed in Balb/c mice. Moreover, cystamine reduced levels of atrial natriuretic peptide (ANP), C-reactive protein (CRP), heart type-fatty acid binding protein (h-FABP), creatine kinase-MB (CK-MB) and IL-6 in LV tissues of NZB/W-F1 mice (p b 0.05). Additionally, in LV tissues of NZB/W-F1 mice, suppression of hypertrophic signaling mediated by IL-6 in response to administration of cystamine was revealed, including phosphorylation of MEK5, ERK5, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) (p b 0.05). Significance: Cystamine alleviated LV hypertrophy in NZB/W-F1 mice as a result of decrease in hypertrophic mediators and suppression of IL-6 mediated hypertrophic signaling.

Research paper thumbnail of Effects of Deep-Seawater on Blood Lipids and Pressure in High-Cholesterol Dietary Mice

Journal of Food Biochemistry, 2010

Three different deep-seawater (DSW) treated by means of reverse osmosis (RO DSW), electrodialysis... more Three different deep-seawater (DSW) treated by means of reverse osmosis (RO DSW), electrodialysis (ED DSW) and 10% (v/v) dilution with ddH 2 O (10% DSW) were as treated groups, while distilled water (NDW) was the control

Research paper thumbnail of IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Gαq interaction and protein kinase C-α/CaMKII activation in H9c2 cardiomyoblast cells

Journal of Endocrinology, 2008

The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor ... more The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2R. In our study of H9c2 cardiomyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure the expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IGF2R overexpression and myocardial infarction. The treatment of H9c...

Research paper thumbnail of Effects of Cystamine on antioxidant activities and regulatory T cells in lupus-prone mice

Journal of Cellular and Molecular Medicine, 2013

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells... more Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4 + /CD25 + regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4 + / CD25 + regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4 + /CD25 + regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.

Research paper thumbnail of Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70kDa U1-snRNP autoantigen

Journal of Biomedical Science, 2010

Background: Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with... more Background: Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure. Methods: To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting. Results: Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1. Conclusions: These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.

Research paper thumbnail of Effects of human parvovirus B19 VP1 unique region protein on macrophage responses

Journal of Biomedical Science, 2009

Background Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of ce... more Background Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage. Methods To investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed. Results In the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein. Conclusion Taken together, our experimental results suggest that B19...

Research paper thumbnail of Japanese Encephalitis Virus Envelope Protein Mitigates TNF-α mRNA Expression in RAW264.7 Cells

Inflammation, 2008

Japanese encephalitis virus (JEV) is known as an important mosquito-borne human pathogen that cau... more Japanese encephalitis virus (JEV) is known as an important mosquito-borne human pathogen that causes Japanese encephalitis and may lead to lethal effect. Since monocyte has been demonstrated to play transmissible role for JEV, rare study is reported to clarify the effect of JEV envelope (JEVE) protein on monocyte. This study intends to investigate the effects of JEVE protein inside monocyte. Notably, significant decreased expression of tumour necrosis factor (TNF)-α mRNA in RAW264.7 cells transfected with pEGFP-JEVE was observed as compared to those cells transfected with pEGFP. Increased p21 Waf1/Cip1 protein was observed in both pEGFP and pEGFP-JEVE transfected RAW264.7 cells. However, increased p53 protein was only detected in pEGFPtransfected cells but not pEGFP-JEVE transfected cells as well as the result that no increased expression of nuclear factor-kB was observed in pEGFP-JEVE transfected cells. These experimental results indicate the effects of JEVE protein in alleviating TNF-α mRNA expression that is associated with the increased p53-independent p21 Waf1/Cip1 expression and provide an explanation in the role of JEV transmission through monocyte.

Research paper thumbnail of Effects of taurine on hepatic lipid metabolism and anti-inflammation in chronic alcohol-fed rats

Food Chemistry, 2012

The effects of taurine (Tau) in regulation of lipid metabolism and decreasing inflammation in chr... more The effects of taurine (Tau) in regulation of lipid metabolism and decreasing inflammation in chronic alcohol-fed rats was investigated. Rats were randomly divided into three groups: (1) isocaloric solution; (2) 3 g alcohol/kg BW/day; (3) 3 g alcohol/kg BW/day + 1 g Tau/kg BW/day for 6 weeks. Liver size and serum/liver lipids of alcohol-fed rats were decreased (p < 0.05) by Tau supplementation, but daily fecal lipid/bile acid outputs were increased (p < 0.05). Regarding de novo lipogenesis, Tau downregulated (p < 0.05) fatty-acid biosynthesis and upregulated (p < 0.05) cholesterol metabolism (CYP7A1) and energy expenditure (PPAR-a). Serum AST and ALT, and hepatic TNF-a levels and MMP-9 activity of alcohol-fed rats were decreased (p < 0.05) by Tau supplementation which may be related to the maintenance of higher (p < 0.05) antioxidant levels (lower thiobarbituric-acid-reactive-substances values and higher trolox equivalent antioxidant capacity) in serum and livers. Our study indicates that Tau downregulates lipogenesis, oxidative stress, and inflammation in chronic alcohol-fed rats.

Research paper thumbnail of Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters

Food Chemistry, 2013

Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxyb... more Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids. To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets. Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9 mL NJ/kg BW, respectively. After a 6-week feeding period, the increased (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) by NJ supplementation. NJ also decreased (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) serum/liver lipids but enhanced (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters. High-fat dietary hamsters supplemented with NJ had higher (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) liver antioxidant capacities but lowered (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) liver iNOS, COX-2, TNF-α, and IL-1β expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ. Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses.

Research paper thumbnail of Taurine alleviates dyslipidemia and liver damage induced by a high-fat/cholesterol-dietary habit

Food Chemistry, 2010

Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Co... more Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Control); high-fat/cholesterol diet (HFCD); HFCD supplemented with 1% Tau (HFCD/1% Tau); HFCD supplemented with 2% Tau (HFCD/2% Tau). Tau supplementation improved (P<0.05) serum lipids and cholesterol profile in the high-fat/cholesterol-dietary hamsters. Although hepatic cholesterol/triacylglycerol in the high-fat/cholesterol-dietary hamsters were not (P>0.05) changed by Tau supplementation, faecal cholesterol and bile acid outputs were increased (P<0.05). Two percent Tau supplementation unregulated (P<0.05) HMG-CoA reductase and cholesterol 7-α hydroxylase (CYP7A1) expressions in the high-fat/cholesterol-dietary hamsters. Besides, Tau supplementation also increased (P<0.05) LDL receptor mRNA expressions in high-fat/cholesterol-dietary hamsters. Tau supplementation also reduced serum GPT and GOT values and C-reactive protein (CRP) levels in the high-fat/cholesterol-dietary hamsters. Results clearly indicated that Tau could alleviate blood lipids and hepatic damage induced by a high-fat/cholesterol-dietary diet.

Research paper thumbnail of Ocimum gratissimumAqueous Extract Protects H9c2 Myocardiac Cells from H2O2-Induced Cell Apoptosis through Akt Signalling

Evidence-Based Complementary and Alternative Medicine, 2011

Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the he... more Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the heart.O. gratissimumis one of the more well-known medicinal plants among theOcimumspecies and widely used in treatment of inflammatory diseases. In this study, we hypothesized that aqueous extract ofO. gratissimumleaf (OGE) may protect myocardiac cell H9c2 from oxidative injury by hydrogen peroxide (H2O2). Our results revealed that OGE pretreatment dose-dependently protects H9c2 cells from cell death when exposed to H2O2. Additionally, DNA condensation induced by H2O2was also reduced by OGE pretreatment, suggesting thatOcimum gratissimumextract may attenuate H2O2-induced chromosome damage. Further investigation showed that OGE pretreatment inhibited H2O2-induced activation of caspase-3 and caspase-9, as well as H2O2-induced upregulation of proapoptotic Apaf-1 and the release of cytosolic cytochrome c, but has little effect on the activation of caspase-8. Additionally, OGE pretreatment sign...

Research paper thumbnail of Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice

European Journal of Pharmacology, 2008

The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patien... more The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE. To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-κB) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE).

Research paper thumbnail of Augmentation of Thermotolerance in Primary Skin Fibroblasts from a Transgenic Pig Overexpressing the Porcine HSP70.2

Asian-Australasian Journal of Animal Sciences, 2005

A high environmental temperature affects the economic performance of pigs. Heat shock protein 70 ... more A high environmental temperature affects the economic performance of pigs. Heat shock protein 70 (HSP70) has been reported to participate importantly in thermotolerance. This study aims to produce transgenic pigs overexpressing porcine HSP70.2, the highly inducible one of HSP70 members, and to prove the cellular thermotolerance in the primary fibroblasts from the transgenics. A recombinant plasmid in which the sequence that encodes the porcine HSP70.2 gene is fused to green fluorescence protein (GFP) was constructed under the control of cytomegalovirus (CMV) enhancer and promoter. Two transgenic pigs were produced by microinjecting pCMV-HSP70-GFP DNA into the pronucleus of fertilized eggs. Immunoblot assay revealed the varied overexpression level (6.4% and 1.4%) of HSP70-GFP in transgenic pigs. After heating at 45°C for 3 h, the survival rate (78.1%) of the primary fibroblast cells from the highly expressing transgenic pig exceeded that from the non-transgenic pig (62.9%). This result showed that primary fibroblasts overexpressing HSP70-GFP confer cell thermotolerance. We suggest that transgenic pigs overexpressing HSP70 might improve their thermotolerance in summer and therefore reduce the economic loss in animal production.

Research paper thumbnail of Hypolipidemic and Antioxidative Effects of Noni (Morinda citrifolia L.) Juice on High- fat/Cholesterol-Dietary Hamsters

Plant Foods for Human Nutrition, 2012

Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and antioxidative e... more Noni juice (NJ) is rich in phytochemicals and polysaccharides. Lipid-lowering and antioxidative effects of NJ were investigated in this study. Fifty male hamsters were assigned randomly to one of the following groups: (1) normal diet and distilled water (LFCD); (2) high-fat/cholesterol diet and distilled water (HFCD); (3) HFCD and 3 ml NJ (including 0.20 g solids)/kg BW (NJ_L); (4) HFCD and 6 mL NJ (including 0.40 g solids)/kg BW (NJ_M); (5) HFCD and 9 ml NJ (including 0.60 g solids)/kg BW (NJ_H) for six weeks. NJ supplementation decreased (p<0.05) serum triacylglycerol, cholesterol, atherogenic index, malondialdehyde levels, and hepatic lipids in HFCD hamsters, whereas serum trolox equivalent antioxidant capacity, glutathione, and fecal lipids in HFCD hamsters were increased (p<0.05) by NJ supplementation. Although NJ supplementation downregulated (p<0.05) sterol regulator element binding protein-1c in HFCD hamsters, it upregulated (p<0.05) hepatic peroxisome proliferatoractivated receptor-alpha and uncoupling protein 2 gene expressions in HFCD hamsters. Results demonstrate that NJ promotes cardioprotection in a high-fat/cholesterol diet.

Research paper thumbnail of Human Parvovirus B19 NS1 Protein Aggravates Liver Injury in NZB/W F1 Mice

PLoS ONE, 2013

Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence... more Human parvovirus B19 (B19) has been associated with a variety of diseases. However, the influence of B19 viral proteins on hepatic injury in SLE is still obscure. To elucidate the effects of B19 viral proteins on livers in SLE, recombinant B19 NS1, VP1u or VP2 proteins were injected subcutaneously into NZB/W F1 mice, respectively. Significant expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected in NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Markedly hepatocyte disarray and lymphocyte infiltration were observed in livers from NZB/WF 1 mice receiving B19 NS1 as compared to those mice receiving PBS. Additionally, significant increases of Tumor Necrosis Factor-a (TNF-a), TNF-a receptor, IkB kinase-a (IKK-a), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IkB) and nuclear factor-kappa B (NF-kB) were detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Accordingly, significant increases of matrix metalloproteinase-9 (MMP9) and Uplasminogen activator (uPA) were also detected in livers from NZB/W F1 mice receiving B19 NS1 as compared to those mice receiving PBS. Contrarily, no significant variation on livers from NZB/W F1 mice receiving B19 VP1u or VP2 was observed as compared to those mice receiving PBS. These findings firstly demonstrated the aggravated effects of B19 NS1 but not VP1u or VP2 protein on hepatic injury and provide a clue in understanding the role of B19 NS1 on hepatic injury in SLE.

Research paper thumbnail of Increased cardiac injury in NZB/W F1 mice received antibody against human parvovirus B19 VP1 unique region protein

Molecular Immunology, 2011

Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and developmen... more Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and development of systemic lupus erythematosus (SLE). However, the influence of anti-B19-VP1u antibodies on cardiac disorders in SLE is still obscure. To elucidate the effects of anti-B19-VP1u IgG in SLE, passive transfer of PBS, normal rabbit IgG or rabbit anti-B19-VP1u IgG was injected intravenously into NZB/W F1 mice, respectively. Significant expression of IL-1β, IL-6 and TNF-α were detected in NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Markedly cardiomyocyte disarray and lymphocyte infiltration were observed in left ventricle of hearts from NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Additionally, significant increases of matrix metalloproteinase-9 (MMP9) activity and protein expression were detected in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. Accordingly, significant increase of phosphorylated p-38 and NF-κB proteins were observed in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. However, no significant variation of cardiac atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), heart-type fatty acid-binding protein (h-FABP) and creatine kinase MB (CK-MB) were detected among all experimental groups. These findings firstly demonstrated the aggravated effects of anti-B19 VP1u IgG on cardiac injury by induction of inflammatory but not myocardial infarction-associated proteins through activation of phosphorylated p-38 and NF-κB signaling.

Research paper thumbnail of Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

PLoS ONE, 2014

As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important huma... more As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-a (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-a or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-a, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity.

Research paper thumbnail of Exacerbating Effects of Human Parvovirus B19 NS1 on Liver Fibrosis in NZB/W F1 Mice

PLoS ONE, 2013

Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts v... more Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-b/Smad fibrotic signaling by increasing the expressions of TGF-b, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and a-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.

Research paper thumbnail of Cardiac Fas Receptor-dependent Apoptotic Pathway in Obese Zucker Rats**

Obesity, 2007

Very limited information regarding the cardiac molecular mechanism in obesity is available. The p... more Very limited information regarding the cardiac molecular mechanism in obesity is available. The purpose of this study was to evaluate the cardiac Fas receptor-dependent (type I) apoptotic pathway in obese Zucker rats. Sixteen obese Zucker rats were studied at 5 to 6 months of age, and 16 age-matched lean Zucker rats served as controls. Heart weight index, myocardial architecture, key components of the Fas receptor-dependent apoptotic pathway, apoptotic activity, and fibrosis in the excised left ventricle of rats were measured by weight scales, hematoxylin and eosin staining, Western blotting, TUNEL assay, and Masson trichrome staining. Body weight, whole heart weight, left ventricular weight, ratio of whole heart weight to tibia length, percentage of TUNEL-positive cardiac myocytes, and percentage of cardiac fibrosis were significantly increased in the obese group. Cardiomyocyte disarray and increased cardiac interstitial space were observed in obese rats. Protein levels of Fas ligand, Fas death receptors, and Fas-associated Death Domain were all significantly increased in the obese group. In addition, pro-caspase-8 and pro-caspase-3 were significantly decreased, whereas activated caspase-8 and activated caspase-3 were significantly increased in the obese group, which implies that pro-forms of caspase-8 and caspase-3 were cleaved into active-forms caspase-8 and caspase-3. Cardiac Fas receptor-dependent apoptotic pathways were more activated in obese rats&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; hearts, which may provide one of the possible apoptotic mechanisms for developing cardiac abnormality in obesity.

Research paper thumbnail of More Activated Cardiac Mitochondrial-dependent Apoptotic Pathway in Obese Zucker Rats**

Obesity, 2007

Obesity is often associated with the development of heart failure, but the precise mechanisms rem... more Obesity is often associated with the development of heart failure, but the precise mechanisms remain uncertain. The purpose of this study was to evaluate the key components of the mitochondrial-dependent apoptotic pathway in excised heart from obese Zucker rats. Twelve obese Zucker rats were studied at 5 to 6 months of age, and 12 age-matched lean Zucker rats served as control. The myocardial architecture and key components of the mitochondrial-dependent apoptotic pathway in the excised left ventricle from rats were measured by histopathological analysis, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR). The ratios of whole heart weight to tibia length were significantly increased in the obese group. Cardiomyocyte disarray, the increased interstitial space, and minor cardiac fibrosis were observed in obese rat hearts. Pro-apoptotic Bcl2 family members, Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3) and Bad levels, were significantly increased in obese rat hearts, whereas anti-apoptotic Bcl2 family member, Bcl2 level, was significantly decreased. Cytosolic cytochrome c indicating cytochrome c release from mitochondria was significantly increased in obese rat heart. In addition, upstream pro-caspase-9 and pro-caspase-3 were significantly decreased, whereas activated caspase-9 and activated caspase-3 were significantly increased in obese rat hearts, compared with lean rat heart, implying that pro-forms of caspase-9 and caspase-3 were cleaved into active-forms caspase-9 and caspase-3. The cardiac mitochondrial-dependent apoptotic pathway was more activated in obese Zucker rats than in lean rats, which may provide one possible apoptotic mechanism for developing heart failure in obesity.

Research paper thumbnail of Cystamine ameliorates ventricular hypertrophy associated with modulation of IL-6-mediated signaling in lupus-prone mice

Life Sciences, 2013

The aim of this study is to investigate the protective effects of cystamine on lupus-associated c... more The aim of this study is to investigate the protective effects of cystamine on lupus-associated cardiac hypertrophy. Main methods: Balb/c and lupus-prone NZB/W-F1 mice were individually randomized into sham group (saline, n = 16) and cystamine group (n = 16). Mice received saline or cystamine (100 mmol in 100 μL saline) by daily intraperitoneal injection for 2 consecutive weeks. Morphological, histological, and biochemical alterations were investigated. Key findings: Cystamine decreased both left ventricular (LV) mass and LV mass/tissue-to-blood ratio (TBR) in NZB/W-F1 mice (p b 0.05), whereas slight effects were observed in Balb/c mice. Moreover, cystamine reduced levels of atrial natriuretic peptide (ANP), C-reactive protein (CRP), heart type-fatty acid binding protein (h-FABP), creatine kinase-MB (CK-MB) and IL-6 in LV tissues of NZB/W-F1 mice (p b 0.05). Additionally, in LV tissues of NZB/W-F1 mice, suppression of hypertrophic signaling mediated by IL-6 in response to administration of cystamine was revealed, including phosphorylation of MEK5, ERK5, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) (p b 0.05). Significance: Cystamine alleviated LV hypertrophy in NZB/W-F1 mice as a result of decrease in hypertrophic mediators and suppression of IL-6 mediated hypertrophic signaling.

Research paper thumbnail of Effects of Deep-Seawater on Blood Lipids and Pressure in High-Cholesterol Dietary Mice

Journal of Food Biochemistry, 2010

Three different deep-seawater (DSW) treated by means of reverse osmosis (RO DSW), electrodialysis... more Three different deep-seawater (DSW) treated by means of reverse osmosis (RO DSW), electrodialysis (ED DSW) and 10% (v/v) dilution with ddH 2 O (10% DSW) were as treated groups, while distilled water (NDW) was the control

Research paper thumbnail of IGF-II/mannose-6-phosphate receptor signaling induced cell hypertrophy and atrial natriuretic peptide/BNP expression via Gαq interaction and protein kinase C-α/CaMKII activation in H9c2 cardiomyoblast cells

Journal of Endocrinology, 2008

The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor ... more The role played by IGF-II in signal transduction through the IGF-II/mannose-6-phosphate receptor (IGF2R) in heart tissue has been poorly understood. In our previous studies, we detected an increased expression of IGF-II and IGF2R in cardiomyocytes that had undergone pathological hypertrophy. We hypothesized that after binding with IGF-II, IGF2R may trigger intracellular signaling cascades involved in the progression of pathologically cardiac hypertrophy. In this study, we used immunohistochemical analysis of the human cardiovascular tissue array to detect expression of IGF2R. In our study of H9c2 cardiomyoblast cell cultures, we used the rhodamine phalloidin staining to measure the cell hypertrophy and western blot to measure the expression of cardiac hypertrophy markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cells treated with IGF-II. We found that a significant association between IGF2R overexpression and myocardial infarction. The treatment of H9c...

Research paper thumbnail of Effects of Cystamine on antioxidant activities and regulatory T cells in lupus-prone mice

Journal of Cellular and Molecular Medicine, 2013

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells... more Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4 + /CD25 + regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4 + / CD25 + regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4 + /CD25 + regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.

Research paper thumbnail of Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70kDa U1-snRNP autoantigen

Journal of Biomedical Science, 2010

Background: Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with... more Background: Human parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure. Methods: To further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting. Results: Significantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1. Conclusions: These findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.

Research paper thumbnail of Effects of human parvovirus B19 VP1 unique region protein on macrophage responses

Journal of Biomedical Science, 2009

Background Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of ce... more Background Activity of secreted phospholipase A (sPLA2) has been implicated in a wide range of cellular responses. However, little is known about the function of human parvovirus B19-VP1 unique region (VP1u) with sPLA2 activity on macrophage. Methods To investigate the roles of B19-VP1u in response to macrophage, phospholipase A2 activity, cell migration assay, phagocytosis activity, metalloproteinase assay, RT-PCR and immunoblotting were performed. Results In the present study, we report that migration, phagocytosis, IL-6, IL-1β mRNA, and MMP9 activity are significantly increased in RAW264.7 cells by B19-VP1u protein with sPLA2 activity, but not by B19-VP1uD175A protein that is mutated and lacks sPLA2 activity. Additionally, significant increases of phosphorylated ERK1/2 and JNK proteins were detected in macrophages that were treated with B19-VP1u protein, but not when they were treated with B19-VP1uD175A protein. Conclusion Taken together, our experimental results suggest that B19...

Research paper thumbnail of Japanese Encephalitis Virus Envelope Protein Mitigates TNF-α mRNA Expression in RAW264.7 Cells

Inflammation, 2008

Japanese encephalitis virus (JEV) is known as an important mosquito-borne human pathogen that cau... more Japanese encephalitis virus (JEV) is known as an important mosquito-borne human pathogen that causes Japanese encephalitis and may lead to lethal effect. Since monocyte has been demonstrated to play transmissible role for JEV, rare study is reported to clarify the effect of JEV envelope (JEVE) protein on monocyte. This study intends to investigate the effects of JEVE protein inside monocyte. Notably, significant decreased expression of tumour necrosis factor (TNF)-α mRNA in RAW264.7 cells transfected with pEGFP-JEVE was observed as compared to those cells transfected with pEGFP. Increased p21 Waf1/Cip1 protein was observed in both pEGFP and pEGFP-JEVE transfected RAW264.7 cells. However, increased p53 protein was only detected in pEGFPtransfected cells but not pEGFP-JEVE transfected cells as well as the result that no increased expression of nuclear factor-kB was observed in pEGFP-JEVE transfected cells. These experimental results indicate the effects of JEVE protein in alleviating TNF-α mRNA expression that is associated with the increased p53-independent p21 Waf1/Cip1 expression and provide an explanation in the role of JEV transmission through monocyte.

Research paper thumbnail of Effects of taurine on hepatic lipid metabolism and anti-inflammation in chronic alcohol-fed rats

Food Chemistry, 2012

The effects of taurine (Tau) in regulation of lipid metabolism and decreasing inflammation in chr... more The effects of taurine (Tau) in regulation of lipid metabolism and decreasing inflammation in chronic alcohol-fed rats was investigated. Rats were randomly divided into three groups: (1) isocaloric solution; (2) 3 g alcohol/kg BW/day; (3) 3 g alcohol/kg BW/day + 1 g Tau/kg BW/day for 6 weeks. Liver size and serum/liver lipids of alcohol-fed rats were decreased (p < 0.05) by Tau supplementation, but daily fecal lipid/bile acid outputs were increased (p < 0.05). Regarding de novo lipogenesis, Tau downregulated (p < 0.05) fatty-acid biosynthesis and upregulated (p < 0.05) cholesterol metabolism (CYP7A1) and energy expenditure (PPAR-a). Serum AST and ALT, and hepatic TNF-a levels and MMP-9 activity of alcohol-fed rats were decreased (p < 0.05) by Tau supplementation which may be related to the maintenance of higher (p < 0.05) antioxidant levels (lower thiobarbituric-acid-reactive-substances values and higher trolox equivalent antioxidant capacity) in serum and livers. Our study indicates that Tau downregulates lipogenesis, oxidative stress, and inflammation in chronic alcohol-fed rats.

Research paper thumbnail of Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters

Food Chemistry, 2013

Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxyb... more Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids. To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets. Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9 mL NJ/kg BW, respectively. After a 6-week feeding period, the increased (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) by NJ supplementation. NJ also decreased (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) serum/liver lipids but enhanced (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters. High-fat dietary hamsters supplemented with NJ had higher (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) liver antioxidant capacities but lowered (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) liver iNOS, COX-2, TNF-α, and IL-1β expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ. Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses.

Research paper thumbnail of Taurine alleviates dyslipidemia and liver damage induced by a high-fat/cholesterol-dietary habit

Food Chemistry, 2010

Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Co... more Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Control); high-fat/cholesterol diet (HFCD); HFCD supplemented with 1% Tau (HFCD/1% Tau); HFCD supplemented with 2% Tau (HFCD/2% Tau). Tau supplementation improved (P<0.05) serum lipids and cholesterol profile in the high-fat/cholesterol-dietary hamsters. Although hepatic cholesterol/triacylglycerol in the high-fat/cholesterol-dietary hamsters were not (P>0.05) changed by Tau supplementation, faecal cholesterol and bile acid outputs were increased (P<0.05). Two percent Tau supplementation unregulated (P<0.05) HMG-CoA reductase and cholesterol 7-α hydroxylase (CYP7A1) expressions in the high-fat/cholesterol-dietary hamsters. Besides, Tau supplementation also increased (P<0.05) LDL receptor mRNA expressions in high-fat/cholesterol-dietary hamsters. Tau supplementation also reduced serum GPT and GOT values and C-reactive protein (CRP) levels in the high-fat/cholesterol-dietary hamsters. Results clearly indicated that Tau could alleviate blood lipids and hepatic damage induced by a high-fat/cholesterol-dietary diet.

Research paper thumbnail of Ocimum gratissimumAqueous Extract Protects H9c2 Myocardiac Cells from H2O2-Induced Cell Apoptosis through Akt Signalling

Evidence-Based Complementary and Alternative Medicine, 2011

Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the he... more Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the heart.O. gratissimumis one of the more well-known medicinal plants among theOcimumspecies and widely used in treatment of inflammatory diseases. In this study, we hypothesized that aqueous extract ofO. gratissimumleaf (OGE) may protect myocardiac cell H9c2 from oxidative injury by hydrogen peroxide (H2O2). Our results revealed that OGE pretreatment dose-dependently protects H9c2 cells from cell death when exposed to H2O2. Additionally, DNA condensation induced by H2O2was also reduced by OGE pretreatment, suggesting thatOcimum gratissimumextract may attenuate H2O2-induced chromosome damage. Further investigation showed that OGE pretreatment inhibited H2O2-induced activation of caspase-3 and caspase-9, as well as H2O2-induced upregulation of proapoptotic Apaf-1 and the release of cytosolic cytochrome c, but has little effect on the activation of caspase-8. Additionally, OGE pretreatment sign...

Research paper thumbnail of Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice

European Journal of Pharmacology, 2008

The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patien... more The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE. To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-κB) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE).