Biomedical subjects

Wan-Sheng Chen

Publications and source records attributed to Wan-Sheng Chen.

10 recordsLinked to original sources

PubMed2007

Cap1p plays regulation roles in redox, energy metabolism and substance transport: an investigation on Candida albicans under normal culture condition.

Cap1p, a transcription factor in Candida albicans, is believed to be required for tolerance to oxidative stress. However, no information is available concerning its function on basal transcriptional profile. In this study, differentially expressed genes between the CAP1-deleted strain and its parental strain under normal culture condition were identified through microarray analysis. Notably, among the 48 down-regulated genes with the deletion of CAP1, there were three clusters, functionally related to intracellular redox, energy metabolism and substance transport. IPF7817, IPF11105 and FDH11, the three putative Cap1p target genes functionally related to redox, were shown to be activated by oxidative stress in a Cap1p-dependent manner. Furthermore, rhodamine 6G efflux analyses demonstrated that Cap1p contributed to the energy-driven efflux. Taken together, these results reveal that Cap1p plays a significant role in redox status regulation, energy metabolism and substance transport under normal culture condition.

Basic-Leucine Zipper Transcription Factors↗

PubMed2006

cDNA microarray analysis of differential gene expression and regulation in clinically drug-resistant isolates of Candida albicans from bone marrow transplanted patients.

Fungi have emerged as the fourth most common pathogens isolated in nosocomial bloodstream infections, and Candida albicans is the most common human fungal pathogen. Only a few antibiotics are effective in the treatment of fungal infections. In addition, the repetition and lengthy duration of fluconazole therapy has led to an increased incidence of azole resistance and treatment failure associated with C. albicans. To investigate the mechanism of drug resistance and explore new targets to treat clinically resistant fungal pathogens, we examined the large-scale gene expression profile of two sets of matched fluconazole-susceptible and -resistant bloodstream C. albicans isolates from bone marrow transplanted (BMT) patients for the first time by microarray analysis. More than 198 differentially expressed genes were identified and they were confirmed and validated by RT-PCR independently. Not surprisingly, the resistant phenotype is associated with increased expression of CDR mRNA, as well as some common genes involved in drug resistance such as CaIFU5, CaRTA2 and CaIFD6. Meanwhile, some special functional groups of genes, including ATP binding cassette (ABC) transporter genes (IPF7530, CaYOR1, CaPXA1), oxidative stress response genes (CaALD5, CaGRP1, CaSOD2, IPF10565), copper transport and iron mobilization-related genes (CaCRD1/2, CaCTR1/2, CaCCC2, CaFET3) were found to be differentially expressed in the resistant isolates. Furthermore, among these differentially expressed genes, some co-regulated with CaCDR1, CaCDR2 and CaIFU5, such as CaPDR16 and CaIFD6, have a DRE-like element and may interact with TAC1 in the promoter region. These findings may shed light on mechanisms of azole resistance in C. albicans and clinical antifungal therapy.

ATP-Binding Cassette Transporters↗

PubMed2006

Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats.

AIM: To investigate the protective effect of steroidal saponins from Anemarrhena asphodeloides (ATS) on ovariectomy (OVX)-induced bone loss. METHODS: Sprague-Dawley rats were divided into sham and OVX groups. The OVX rats were treated with vehicle, nylestriol or steroidal saponins extract for 12 weeks. Serum calcium, phosphorus, estradiol (E(2)), osteocalcin concentration and serum alkaline phosphatase activity were measured. Bone density was assayed by dual-energy X-ray absorptiometry. The undecalcified longitudinal proximal tibial metaphysical (PTM) sections were cut and stained for histomorphometric analysis of the bone. RESULTS: In OVX rats, alkaline phosphatase activities in serum were markedly increased and concentrations of osteocalcin were decreased by ATS treatment, which had no influence on the body weight. Meanwhile, atrophy of the uterus and descent of bone mineral density (BMD) was suppressed by treatment with ATS. In addition, ATS completely corrected the decreased the concentration of calcium and E(2) in serum observed in OVX rats. Histological results showed ATS prevented decreases in trabecular thickness and increases in trabecular separation of proximal tibia metaphysis (PTM) in OVX rats. However, it did not alter osteoclast number in OVX rats. Moreover, ATS (300 mg/kg) had a remarkable effect on promoting bone formation action in OVX rats. Nylestriol treatment decreased the bone formation rate and mineral apposition rate. CONCLUSION: An adequate supply of steroidal saponins of Anemarrhena asphodeloides prevented OVX-induced bone loss in rats through the promotion of bone formation but not the inhibition of bone resorption.

Alkaline Phosphatase↗

PubMed2005

Cap1p is involved in multiple pathways of oxidative stress response in Candida albicans.

Cap1p, a transcription factor in Candida albicans, is thought to participate in oxidative stress tolerance, but the pathways involved are still unclear. The study was designed to reveal the possible pathways by examining changes in the transcription profile after H2O2 treatment with both the cap1-deleted strain CJD21 and its parental strain CAI4 using microarray analysis. Of the identified 89 genes differentially expressed in CAI4 after exposure to H2O2, 76 genes were in a Cap1p-dependent expression pattern. We have shown that Cap1p is involved in the oxidative stress response in C. albicans via multiple pathways, including the cellular antioxidant defense system (e.g., thioredoxin reductase, glutathione reductase, glutathione S-transferase), carbohydrate metabolism and energy metabolism (e.g., glucose-6-phosphate dehydrogenase, transaldolase, glyoxalase I, NADH-dependent flavin oxidoreductase), protein degradation (e.g., 26S proteasome regulatory subunit, ubiquitin-specific protease), ATP-dependent RNA helicase (e.g., DEAD box protein ATP-dependent RNA helicase), and resistance pathways (e.g., multidrug resistance protein, ABC transporter essential for cadmium resistance). Real-time reverse transcription-PCR analysis further confirmed the results of microarray. Collectively, this study provides new insight into the biological functions of Cap1p in oxidative stress response.

Basic-Leucine Zipper Transcription Factors↗

PubMed2005

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum.

Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of Polygonum multiflorum Thunb., one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg). Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF) protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.

Animals↗

PubMed2005

cDNA array analysis of the differential expression change in virulence-related genes during the development of resistance in Candida albicans.

Candida albicans is the most frequently isolated fungus in immunocompromised patients associated with mucosal and deep-tissue infections. To investigate the correlation between virulence and resistance on a gene expression profile in C. albicans, we examined the changes in virulence-related genes during the development of resistance in C. albicans from bone marrow transplant patients using a constructed cDNA array representing 3096 unigenes. In addition to the genes known to be associated with azole resistance, 16 virulence-related genes were identified, whose differential expressions were newly found to be associated with the resistant phenotype. Differential expressions for these genes were confirmed by RT-PCR independently. Furthermore, the up-regulation of EFG1, CPH2, TEC1, CDC24, SAP10, ALS9, SNF1, SPO72 and BDF1, and the down-regulation of RAD32, IPF3636 and UBI4 resulted in stronger virulence and invasiveness in the resistant isolates compared with susceptible ones. These findings provide a link between the expression of virulence genes and development of resistance during C. albicans infection in bone marrow transplant (BMT) patients, where C. albicans induces hyphal formation and expression change in multiple virulence factors.

Candida albicans↗

PubMed2005

cDNA microarray analysis of differential gene expression in Candida albicans biofilm exposed to farnesol.

Candida albicans biofilms are structured microbial communities with high levels of drug resistance. Farnesol, a quorum-sensing molecule that inhibits hyphal formation in C. albicans, has been found to prevent biofilm formation by C. albicans. There is limited information, however, about the molecular mechanism of farnesol against biofilm formation. We used cDNA microarray analysis to identify the changes in the gene expression profile of a C. albicans biofilm inhibited by farnesol. Confocal scanning laser microscopy was used to visualize and confirm normal and farnesol-inhibited biofilms. A total of 274 genes were identified as responsive, with 104 genes up-regulated and 170 genes down-regulated. Independent reverse transcription-PCR analysis was used to confirm the important changes detected by microarray analysis. In addition to hyphal formation-associated genes (e.g., TUP1, CRK1, and PDE2), a number of other genes with roles related to drug resistance (e.g., FCR1 and PDR16), cell wall maintenance (e.g., CHT2 and CHT3), and iron transport (e.g., FTR2) were responsive, as were several genes encoding heat shock proteins (e.g., HSP70, HSP90, HSP104, CaMSI3, and SSA2). Further study of these differentially regulated genes is warranted to evaluate how they may be involved in C. albicans biofilm formation. Consistent with the down-regulation of the cell surface hydrophobicity-associated gene (CSH1), the water-hydrocarbon two-phase assay showed a decrease in cell surface hydrophobicity in the farnesol-treated group compared to that in the control group. Our data provide new insight into the molecular mechanism of farnesol against C. albicans biofilm formation.

Biofilms↗

PubMed2005

[Coumarins from root of Zanthoxylum dimorphophyllum var. spinifolium].

OBJECTIVE: To study the chemical components from dried roots of Zanthoxylum dimorphophyllum var. spinifoliun. METHOD: The chemical components were isolated by low pressure column chromatography and their structures were identified by spectroscopic methods. RESULT: Five compounds were isolated and identified as 6-(2', 3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-5-methoxy-2H-1-benzopyran-2-one (I), 6-(2',3'-dihydroxy-3'-methyl-butyl)-7-methoxy-8-(3'-methyl-but-2'-enyl)-2H-1-benzopyran-2-one (II),6-(2',3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-2H-1-benzopyran-2-one (III), 6-(2', 3'-oxiranyl-3'-methyl-butyl)-7-methoxy-8- (3-methyl-but-2-enyl)-2H-1-benzopyran-2-one (IV), 7-methoxy-8-(3'-methyl-but-2'-enyl)-2H-1-benzopyran-2-one (V). CONCLUSION: These compounds were isolated from the plant for the first time.

Coumarins↗

PubMed2004

New triterpenoid saponins from bulbs of Bolbostemma paniculatum.

Nine new triterpenoid saponins were isolated from the bulbs of Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae): 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24 E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,18,20,26-tetrahydroxy-(20S)-dammar-24E-en-3-O-alpha-L-arabinopyranosyl-(1-->2)-beta-D-(6-acetyl)glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-(20S)-dammar-24E-en-3-O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-8-formyl-(20S)-dammar-24E-en-3-O-alpha-L-(3-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside, 7beta,20,26-trihydroxy-8-formyl-(20S)-dammar-24E-en-3- O-alpha-L-(4-acetyl)arabinopyranosyl-(1-->2)-beta-D-glucopyranoside and 6'-O-palmitoyltubeimoside I. In addition, four known triterpenoid saponins: tubeimoside I, tubeimoside II, tubeimoside III and tubeimoside IV were isolated. The structures of the above compounds were elucidated based on spectroscopic studies, and the configuration of C-20 of tubeimoside IV was revised as S rather than R as reported in previous literature. The compounds were tested for their antiviral activity

Acyclovir↗

PubMed2003

[Studies on the coumarins in the root of Zanthoxylum dimorphophyllum].

OBJECTIVE: To study the chemical constituents of the dried roots of Zanthoxylum dimorphophyllumr. spinifolium and to find out the active constituents of the plant. METHOD: Modern chromatography was used to purify chemical constituents, and their structures were identified by various spectral methods. RESULT: Four compounds were isolated and identified as isopimpinellin (I), xanthoxyletin (II), 6-(2', 3'-dihydroxy-3'-methyl-butyl)-7-hydroxy-2H-1-benzopyran-2-one (III), 6-(2'-O-beta-D-glucopyranosyloxy, 3'-dihydroxy-3'-methybutyl)-7-hydroxy-2H-1-benzopyran-2-one (IV). CONCLUSION: All of the above compounds were isolated from the above mentioned plant for the first time.

Coumarins↗