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1.  Association of intercellular adhesion molecular-1 gene polymorphism in ischemic stroke patients 
Ischemic stroke (IS) is a prevalent disease causing a body disability, the third leading cause of death in Taiwan. It shows that the level of intercellular adhesion molecular-1 (ICAM-1) in IS patients is higher than control subjects.
This study is to investigate the possible association of ICAM-1 (G1548A) polymorphism in IS patients.
Materials and Methods:
A total of 646 subjects were enrolled in this study, including 312 IS patients, and 334 controls without a history of symptomatic IS. The ICAM-1 (G1548A) polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Clinical factors were also determined.
The frequencies of the ICAM-1 (G1548A) polymorphism for G/G, G/A, and A/A were 74.8%, 23.9%, and 0.3%, respectively, in healthy controls, and 62.8%, 32.1%, and 5.1%, respectively, in patients. The frequency of the ICAM-1 (G1548A) A allele (21.2% versus 13.2%, respectively; P = 0.007) and the carriers of the ICAM-1 (G1548A) A allele (37.2% versus 25.2%; P = 0.019, OR 1.76, 95% CI 1.1-2.83) are great in IS patients compared with healthy controls. There is a higher risk of IS associated with homozygosity for the ICAM-1 (G1548A) A allele (AA genotype) compared with the control population (5.1% vs. 0.3%, respectively, P = 0.04; OR 5.1, 95% CI 1.19-21.66). We also observed both hypertension and diabetes has shown a positive association with IS.
The ICAM-1 (G1548A) polymorphism was associated with independent risk factor for the development of IS.
PMCID: PMC3788285  PMID: 24101821
Allele; intercellular adhesion molecular-1; ischemic stroke; polymorphism
2.  Interleukin-1 receptor antagonist gene polymorphism in patients with multidrug-resistant Acinetobacter baumannii-associated pneumonia 
Annals of Thoracic Medicine  2012;7(2):74-77.
Multidrug-resistant Acinetobacter baumannii (MDRAB)-associated pneumonia has been a common disease and a therapeutic problem in hospitals. Interleukin-1 receptor antagonist (IL-1ra) has been considered a required role for host immune defense in pneumonia disease. The aim of this study was to investigate whether the variable nucleotide tandem repeat polymorphism of the IL-1ra gene was associated with MDRAB-related pneumonia.
Sixty-six pneumonia patients were enrolled in the study: 36 subjects had MDRAB-related pneumonia and 30 controls had non-MDRAB pneumonia. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the IL-1ra genotype.
The frequencies of the IL-1ra genotype in the MDRAB-related pneumonia cases were A1/A1, 0.889 and A1/A2, 0.111; the frequencies of the IL-1ra genotype in the controls were A1/A1, 0.333 and A1/A2, 0.667. A statistically significant difference was determined (P < 0.05). We also observed an increase in the frequency of IL-1ra A1 allele in the MDRAB-related pneumonia group. A statistically significant difference was determined (P<0.05).
We suggested that IL-1ra polymorphism was associated with the risk of MDRAB-related pneumonia.
PMCID: PMC3339207  PMID: 22558011
Acinetobacter baumannii; IL-1ra; pneumonia; polymorphism
3.  Evaluation of anti-inflammatory effects of Broussonetia papyrifera stem bark 
Indian Journal of Pharmacology  2012;44(1):26-30.
Broussonetia papyrifera is used as a traditional medicine to treat few diseases. However, the antiinflammatory effect of B. papyrifera stem bark has not been evaluated. The aim of this study is to investigate the effects of n-hexane fraction from methanol extract of B. papyrifera stem bark on lipopolysaccharide (LPS)-stimulated inflammation using RAW 264.7 cells.
Materials and Methods:
Methanol extract was obtained from B. papyrifera stem bark and its sequential fractions (hexane, dichloromathane, ethyl acetate, butanol, and aqueous) were obtained by extraction in solvents with increasing polarity and were examined in RAW 264.7 cells.
The secretion profiles of pro-inflammatory parameters, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were found to be significantly reduced in 10-80 μg/ml dose ranges of n-hexane fraction (BP-H) from methanol extract of B. papyrifera stem bark. The expressions of inducible NO synthase (iNOS) was also significantly inhibited by BP-H. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that BP-H treatment decreased LPS-induced iNOS mRNA expression in RAW 264.7 cells.
The results suggest that the B. papyrifera stem bark has anti-inflammatory activity which inhibits the NO production and proinflammatory cytokines in RAW 264.7 cells. B. papyrifera stem bark might act as a potential therapeutic agent for inflammatory diseases.
PMCID: PMC3271534  PMID: 22345865
Anti-inflammatory; Broussonetia papyrifera; hexane; inducible NO synthase; lipopolysaccharide
4.  Association of interleukin-1 beta (-511C/T) polymorphisms with osteoporosis in postmenopausal women 
Annals of Saudi Medicine  2010;30(6):437-441.
Osteoporosis is a common disease of the elderly, in which genetic and clinical factors contribute to the disease phenotype. Since the production of interleukin-1 (IL-1) has been implicated in the bone mass and skeletal disorders, we investigated whether IL-1 system gene polymorphisms are associated with the pathogenesis of osteoporosis in postmenopausal Taiwanese women.
Osteoporosis is diagnosed by dual-energy x-ray absorptiometry, which measures bone mineral density (BMD) at multiple skeletal sites. We studied the IL-1α (-889C/T), IL-1β (-511C/T) and the 86 base pair variable number tandem repeat (VNTR) in intron 2 of the IL-1 receptor antagonist (IL-1ra) gene in 117 postmenopausal women with osteoporosis and 135 control subjects without a history of symptomatic osteoporosis. These gene polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymerase. Blood sugar and other risk factors were also determined.
The frequencies of IL-1β (-511C/T) genotypes (P=.022, odds ratio=1.972) and alleles (P=.02, odds ratio=2.909) showed a statistically significant difference between the two groups. However, we did not find any statistically significant difference in IL-1α and IL-1ra polymorphisms (P>.05). We also observed a positive relationship between osteoporosis and cholesterol and a weak inverse relationship between blood sugar and osteoporosis in postmenopausal women.
These experimental results suggest that the pathogenesis of osteoporosis is associated with IL-1β (-511C/T) polymorphism in postmenopausal women. This polymorphism is an independent risk factor for osteoporosis.
PMCID: PMC2994158  PMID: 20940514
5.  Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages 
British Journal of Pharmacology  2003;140(6):1077-1087.
Although capsaicin analogs might be a potential strategy to manipulate inflammation, the mechanism is still unclear. In this study, the effects and action mechanisms of vanilloid analogs on iNOS and COX-2 expression were investigated in RAW264.7 macrophages.Capsaicin and resiniferatoxin (RTX) can inhibit LPS- and IFN-γ-mediated NO production, and iNOS protein and mRNA expression with similar IC50 values of around 10 μM.Capsaicin also transcriptionally inhibited LPS- and PMA-induced COX-2 expression and PGE2 production. However, this effect exhibited a higher potency (IC50: 0.2 μM), and RTX failed to elicit such responses at 10 μM.Interestingly, we found that capsazepine, a competitive TRPV1 antagonist, did not prevent the inhibition elicited by capsaicin or RTX. Nevertheless, it mimicked vanilloids in inhibiting iNOS/NO and COX-2/PGE2 induction with an IC50 value of 3 μM. RT–PCR and immunoblotting analysis excluded the expression of TRPV1 in RAW264.7 macrophages.The DNA binding assay demonstrated the abilities of vanilloids to inhibit LPS-elicited NF-κB and AP-1 activation and IFN-γ-elicited STAT1 activation. The reporter assay of AP-1 activity also supported this action.The kinase assay indicated that ERK, JNK, and IKK activation by LPS were inhibited by vanilloids.In conclusion, vanilloids can modulate the expression of inflammatory iNOS and COX-2 genes in macrophages through interference with upstream signalling events of LPS and IFN-γ. These findings provide new insights into the potential benefits of the active ingredient in hot chilli peppers in inflammatory conditions.
PMCID: PMC1574120  PMID: 14530214
Capsaicin; capsazepine; TRPV1; macrophages; NO; COX-2; ERK; JNK; IKK

Results 1-5 (5)