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ABSTRACT: Only a small proportion of women infected with human papillomavirus type 18 (HPV18) may progress to persistent infection and cervical neoplasia. This community-based cohort study aimed to assess associations with human leukocyte antigen (HLA) class II genotypes for natural infection of HPV18 and subsequent risk of cervical neoplasia.
Among 10,190 cytologically normal participants, 125 with HPV18 infection were identified by HPV blot kit. HPV18 viral load at study entry was examined by real-time polymerase chain reaction; persistent infection was defined as HPV18 infection at 2 consecutive examinations.
There was a significant association between HLA-DRB1*0403 allele and high HPV18 viral load (>1000 copies in 50 ng of total DNA) at study entry (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection (OR, 13.3; 95% CI, 1.7-105.9). HLA-DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5).
HLA-DRB1*0403 allele and HLA-DRB1*0405-DQA1*0301-DQB1*0302 haplotype may play important roles in determination of high viral load and persistent infection of HPV18 and subsequent cervical neoplasia risk.
Cancer 06/2011; 118(1):223-31. · 4.77 Impact Factor
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ABSTRACT: Taiwanofungus camphoratus (T. camphoratus), a fungus and a Taiwan-specific, well-known traditional Chinese medicine, has long been used to treat diarrhea, hypertension, itchy skin, and liver cancer. To gain a large amount of T. camphoratus, several culture techniques have been developed, including solid-state culture and liquid-state fermentation. Peroxisome proliferator-activated receptor gamma (PPARgamma) has been described as a hypoglycemic agent that increases insulin sensitivity in peripheral tissues and results in reduced blood glucose, insulin, and triglyceride levels in insulin-resistant animals and in type-2 (non-insulin-dependent) diabetic patients. In this study, we investigate the possibility that T. camphoratus might activate PPARgamma in vitro and hypolipidemic activity in vivo. The results show that an aqueous extract of the wild fruiting bodies of T. camphoratus was able to increase the PPARgamma activity in cells transfected with the PPARgamma expression plasmid and the AOx-TK reporter plasmid. Based on the cell experiment, we examined the hypolipidemic effect of wild fruiting bodies (WFT) and a solid-state culture (SST) of T. camphoratus on SD rats fed on a high-cholesterol (HC) diet. The results show that WFT significantly decreased the serum triglyceride level, but could not affect the cholesterol level. SST only slightly decreased the serum triglyceride level. In addition, both WFT and SST significantly decreased the serum alanine transaminase (ALT) level and protected against the liver damage induced by the HC diet from the results of a histological examination. These results suggest that T. camphoratus might contain PPARgamma ligands and result in a hypotriglyceridemic effect, and that it also exhibits a liver protective activity.
Bioscience Biotechnology and Biochemistry 08/2008; 72(7):1704-13. · 1.28 Impact Factor
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ABSTRACT: Chemotherapeutic drugs are usually designed to induce cancer cell death via cell cycle arrest and/or apoptosis pathways. In this study, we used the chemical drug 15,16-dihydrotanshinone I (DHTS) to inhibit breast cancer cell proliferation and tumor growth, and investigate the underlying molecular mechanisms. Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose-dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis. The fact that DHTS-induced apoptosis could be blocked by pretreating cells with pan-caspase inhibitor confirmed that it is mediated through activation of the caspase-3-dependent pathway. In a nude mice xenograft experiment, DHTS significantly inhibited the tumor growth of MDA-MB-231 cells. Taken together, these results suggest that DHTS can inhibit human breast cancer cell proliferation and tumor growth, and might have potential chemotherapeutic applications.
Biochemical Pharmacology 01/2008; 74(11):1575-86. · 4.70 Impact Factor
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Der-Zen Liu,
Hong-Jen Liang,
Chien-Ho Chen,
Ching-Hua Su,
Tzong-Huei Lee,
Chun-Ting Huang,
Wen-Chi Hou,
Shyr-Yi Lin,
Wen-Bin Zhong, Pei-Jung Lin,
Ling-Fang Hung,
Yu-Chih Liang
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ABSTRACT: Taiwanofungus camphoratus (syn. Antrodia camphorata), a medicinal mushroom in Taiwan, is reputed to provide several therapeutic benefits, but the wild fruiting body is very rare. In this study, we used Taiwanofungus camphoratus extracts from wild fruiting bodies and two types of artificial cultivation (solid-state culture and liquid-state fermentation) to examine their anti-inflammatory effects in microglia cells and their possible roles in protection against neurodegenerative diseases. First, EOC13.31 microglia was treated with various kinds of Taiwanofungus camphoratus extracts and lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) to evaluate the iNOS expression. Western blot and RT-PCR analysis showed that among the various kinds of extracts from wild fruiting bodies, methanol extracts were the most potent inhibitors of iNOS expression. Secondly, the potency of methanol extracts could be ranked as follows: extracts of wild fruiting body>solid-state culture>liquid-state fermentation. To clarify the mechanisms involved, methanol extracts from fruiting body were found to inhibit the phosphorylation of extracellular signal-regulated protein kinases (ERK), c-Jun NH2-terminal protein kinases (JNK) and signal transducer and activator of transcription-1 (STAT-1) induced by LPS/IFN-gamma. Methanol extracts from fruiting body also inhibited NF-kappaB activation through the prevention of inhibitor kappaB (IkappaB) degradation. Moreover, methanol extracts from wild fruiting body inhibited both the iNOS and cyclooxygenase-2 (COX-2) expression induced by beta-amyloid in microglia in a dose-dependent manner. In an animal model, we confirmed that methanol extracts from fruiting bodies were able to suppress ear edema, indicating that they have anti-inflammatory activity in vivo. These results suggest that Taiwanofungus camphoratus exhibits an anti-inflammatory activity that might contribute to the prevention of neurodegenerative diseases.
Journal of Ethnopharmacology 08/2007; 113(1):45-53. · 3.01 Impact Factor
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Der-Zen Liu,
Hong-Jen Liang,
Chien-Ho Chen,
Shyr-Yi Lin,
Wen-Bin Zhong,
Feng-Ming Ho,
Wen-Chi Hou,
Jui-Lien Lo,
Yuan-Soon Ho, Pei-Jung Lin,
Ling-Fang Hung,
Yu-Chih Liang
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ABSTRACT: Phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P(2)) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI(3)K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P(3) and inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI(3)K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P(3) production and iNOS expression in LPS-activated macrophages. Inhibition of PI(3)K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI(3)K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-kappaB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI(3)K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway.
Biochimica et Biophysica Acta 07/2007; 1773(6):869-79. · 4.66 Impact Factor
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ABSTRACT: Effects of rolipram, a selective inhibitor of phosphodiesterases (PDE) IV, on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of the giant African snail (Achatina fulica Ferussac). Oscillations of membrane potential bursts were elicited by rolipram and forskolin. The bursts of potential elicited by rolipram were not inhibited after administration with (a) calcium-free solution, (b) high-magnesium solution (30 mM) or (c) U73122. However, the bursts of potential elicited by rolipram were inhibited by pretreatment with KT-5720 (10 microM). Voltage-clamp studies revealed that rolipram decreased the total inward current and steady-state outward currents of the RP4 neuron. The negative slope resistance (NSR) was not detectable in control or rolipram treated RP4 neurons. TEA elicited action potential bursts and an NSR at membrane potential between -50 mV and -30 mV. It is suggested that the bursts of potential elicited by rolipram were not due to (1) synaptic effects of neurotransmitters; (2) NSR of steady-state I-V curve; (3) phospholipase activity of the neuron. The rolipram-elicited bursts of potential were dependent on the phosphodiesterases inhibitory activity and the cAMP signaling pathway in the neuron.
Experimental Neurology 09/2005; 194(2):384-92. · 4.70 Impact Factor
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ABSTRACT: The effects of 2,3-butanedione monoxime (BDM) on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of giant African snail (Achatina fulica Ferussac). The effect of okadaic acid on the neuron was also tested. The RP4 neuron showed a spontaneous firing of action potential. Okadaic acid (1 micromol/l) did not alter the frequency of spontaneous action potential while BDM (3 mmol/l) reversibly elicited bursts of potential (BoP) of the RP4 neuron. The BoP elicited by BDM (3 mmol/l) were reversed 20 min after incubation with diazoxide (500 micromol/l) while the BoP were not altered in preparations treated with okadaic acid and BDM. The BDM-elicited BoP were not inhibited after administration with (a) hexamethonium (100 micromol/l), (b) atropine (1 mmol/l), (c) d-tubocurarine (100 micromol/l), (d) prazosin (100 micromol/l), (e) propranolol (100 micromol/l), (f) calcium-free solution, (g) high K(+) (12 mmol/l) or (h) with high Mg(2+) (30 mmol/l) solutions. The BDM-elicited BoP were inhibited by pretreatment with KT-5720 (10 micromol/l) or H89 (10 micromol/l), the protein kinase A inhibitors. However, the BoP were not affected after application of chelerythrine (10 micromol/l) or Ro 31-8220 (10 micromol/l), the protein kinase C inhibitors. Voltage-clamped studies revealed that BDM elicited a negative slope resistance (NSR) at membrane potentials between -50 and -10 mV. The NSR was not detectable at the same membrane potential in control RP4 neuron. It is suggested that the BoP elicited by BDM were not due to (1) the synaptic effects of neurotransmitters; (2) the activation of cholinergic, adrenergic receptors, or (3) phosphatase activity of the neuron. The BDM-elicited BoP were dependent on the protein kinase A related cAMP in the neuron and the delayed outward K(+) current may contribute to the BDM-elicited BoP.
Pharmacology 03/2005; 73(2):57-69. · 1.79 Impact Factor
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ABSTRACT: Previous serotyping in Chinese patients has failed to confirm an association between HLA-Cw6 and psoriasis. As serotyping has proved to be less valuable in the determination of HLA-C, genotyping of HLA-C in 68 Taiwanese psoriasis vulgaris (PSV) patients was performed using polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR-SSOPH) of HLA-Cw genes. Compared to 213 non-PSV control subjects, HLA-Cw6 was significantly associated with PSV (16.18% of PSV patients vs 5.16% of controls; odds ratio 3.53, Pc</=10(-4)). The amino acid residues on the heavy chain of the HLA-Cw antigens from exon one to exon five were also analyzed. Asp 9, Ser 24, Ala 73, Asp 90, Trp 97, Trp 156 and Asn 77/Lys 80 were found to be positively associated with PSV ( Pc</=0.0044, 0.0008, 0.0026, 0.0014, 0.039, 0.0020 and 0.0000, respectively).
Archives for Dermatological Research 07/2002; 294(5):214-20. · 2.28 Impact Factor
