Biomedical subjects

Feng Chen

Publications and source records attributed to Feng Chen.

At least 37 records · Page 2Linked to original sources

PubMed2006

Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and Mammalian cells.

Resveratrol is a naturally occurring defense compound produced by a limited number of plants in response to stresses. Besides cardiovascular benefits, this health-promoting compound has been reported to extend life spans in yeasts, flies, worms, and fish. To biosynthesize resveratrol de novo, tyrosine ammonia lyase (TAL), 4-coumarate CoA-ligase (4CL), and stilbene synthase (STS) were isolated from Rhodobacter sphaeroides, Arabidopsis thaliana, and Vitis vinifera, respectively. Yeast cells expressing 4CL and STS produce resveratrol when fed with 4-coumaric acid, the substrate of 4CL. When a translational fusion protein joining 4CL and STS was used, yeast cells produced 15-fold more resveratrol than the cotransformed cells, suggesting that physical localization of 4CL and STS facilitate resveratrol production. When the resveratrol pathway was introduced into human HEK293 cells, de novo biosynthesis was detected, leading to intracellular accumulation of resveratrol. We successfully engineered an entire plant natural product pathway into a mammalian host.

Acyltransferases↗

PubMed2006

Robust analysis of 5'-transcript ends (5'-RATE): a novel technique for transcriptome analysis and genome annotation.

Complicated cloning procedures and the high cost of sequencing have inhibited the wide application of serial analysis of gene expression and massively parallel signature sequencing for genome-wide transcriptome profiling of complex genomes. Here we describe a new method called robust analysis of 5'-transcript ends (5'-RATE) for rapid and cost-effective isolation of long 5' transcript ends (approximately 80 bp). It consists of three major steps including 5'-oligocapping of mRNA, NlaIII tag and ditag generation, and pyrosequencing of NlaIII tags. Complicated steps, such as purification and cloning of concatemers, colony picking and plasmid DNA purification, are eliminated and the conventional Sanger sequencing method is replaced with the newly developed pyrosequencing method. Sequence analysis of a maize 5'-RATE library revealed complex alternative transcription start sites and a 5' poly(A) tail in maize transcripts. Our results demonstrate that 5'-RATE is a simple, fast and cost-effective method for transcriptome analysis and genome annotation of complex genomes.

5' Untranslated Regions↗

PubMed2006

Dopamine transporter and D2 receptor binding densities in mice prone or resistant to chronic high fat diet-induced obesity.

This study examined the density of dopamine transporter (DAT) and D2 receptors in the brains of chronic high-fat diet-induced obese (cDIO), obese-resistant (cDR) and low-fat-fed (LF) control mice. Significantly decreased DAT densities were observed in cDR mice compared to cDIO and LF mice, primarily in the nucleus accumbens, striatal and hypothalamic regions. D2 receptor density was significantly lower in the rostral part of caudate putamen in cDIO mice compared to cDR and LF mice.

Analysis of Variance↗

PubMed2006

Effect of methyl jasmonate on phenolics, isothiocyanate, and metabolic enzymes in radish sprout (Raphanus sativus L.).

The effect of spraying exogenous plant hormone methyl jasmonate (MeJA) upon radish sprout (Raphanus sativus L.) was investigated in aspects of total phenolic content (TPC), isothiocyanate content, antioxidant activity of the radish extract, and enzymatic activities of phenylalanine ammonia lyase (PAL) and myrosinase. The MeJA treatment significantly increased the TPC that resulted in the increased DPPH* (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging capacity. In addition, the PAL activity also increased by 60% at 24 h after MeJA treatment. However, the same treatment decreased the amount of 4-methylthio-3-butenylisothiocyanate (MTBITC), a major isothiocyanate in radish sprout and the activity of myrosinase, an enzyme related to produce isothiocyanates.

Acetates↗

PubMed2006

No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: result from a cross-sectional study in a high-risk region of China.

Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases.

Adult↗

PubMed2006

Glucose tolerance normalization following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic ZDF rats.

Pancreas or pancreatic islet transplantation in humans is limited by organ availability, and success of the latter is negatively impacted upon by tissue loss post-transplantation and limited potential for expansion of beta cells. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats engraft without the need for host immune-suppression and normalize glucose tolerance. Here we show long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into diabetic ZDF rats, a model for type 2 diabetes. Porcine insulin is present in circulation after an oral glucose load. Glucose tolerance is normalized in transplanted ZDF hosts and insulin sensitivity restored in formerly diabetic ZDF males. Release of porcine insulin in vitro from tissue originating in transplanted rats occurs within 1 min of glucose stimulation characteristic of first-phase secretion from beta cells. Of potential importance for application of this transplantation technology to treatment of type 2 diabetes in humans and confirmatory of our previous findings in Lewis rats, no host immunosuppression is required for engraftment of E28 pig pancreatic primordia.

Animals↗

PubMed2006

The endo-beta-mannanase gene families in Arabidopsis, rice, and poplar.

Mannans are widespread hemicellulosic polysaccharides in plant cell walls. Hydrolysis of the internal beta-1,4-D: -mannopyranosyl linkage in the backbone of mannans is catalyzed by endo-beta-mannanase. Plant endo-beta-mannanase has been well studied for its function in seed germination. Its involvement in other plant biological processes, however, remains poorly characterized or elusive. The completed genome sequences of Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), and poplar (Populus trichocarpa) provide an opportunity to conduct comparative genomic analysis of endo-beta-mannanase genes in these three species. In silico sequence analysis led to the identification of eight, nine and 11 endo-beta-mannanase genes in the genomes of Arabidopsis, rice, and poplar, respectively. Sequence comparisons revealed the conserved amino acids and motifs that are critical for the active site of endo-beta-mannanases. Intron/exon structure analysis in conjunction with phylogenetic analysis implied that both intron gain and intron loss has played roles in the evolution of endo-beta-mannanase genes. The phylogenetic analysis that included the endo-beta-mannanases from plants and other organisms implied that plant endo-beta-mannanases have an ancient evolutionary origin. Comprehensive expression analysis of all Arabidopsis and rice endo-beta-mannanase genes showed divergent expression patterns of individual genes, suggesting that the enzymes encoded by these genes, while carrying out the same biochemical reaction, are involved in diverse biological processes.

Amino Acid Sequence↗

PubMed2006

Influences of acids and salts on the crystalline phase and morphology of TiO2 prepared under ultrasound irradiation.

Nanocrystalline TiO2 powders were rapidly prepared by hydrolysis of Ti(OC4H9)4 under ultrasound irradiation. The influences of acids (HCl, HNO3, and H2SO4) and their corresponding salts (NaCl, KNO3, and Na2SO4) on the crystalline phase and morphology of products were investigated, respectively. Compared with NaCl and KNO3 that show no evident influence on the crystalline phase, HCl and HNO3 have a decisive influence on the crystalline phase of the products. However, both H2SO4 and Na2SO4 are favorable for the formation of anatase. By adjusting the concentration of SO2-(4) in the reaction medium, the contents of anatase and rutile phases in the TiO2 powders can be successfully controlled. The morphology of TiO2 crystallites are shown to be strongly related to the type of acid used in the reaction medium.

Journal Article↗

PubMed2006

Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors.

Paclitaxel is a widely used naturally occurring antineoplastic agent that has shown great promise in the treatment of a variety of human solid tumors, particularly for advanced breast and ovarian cancers. Recent studies in our laboratory discovered that glucocorticoids could selectively inhibit paclitaxel-induced apoptosis in a number of human solid tumor cell lines in vitro. Since glucocorticoids (such as dexamethasone) are routinely used as a premedication in the clinical application of paclitaxel to prevent hypersensitivity reactions and other adverse effects, the inhibitory effect of glucocorticoids on paclitaxel-induced apoptosis has raised a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with the therapeutic efficacy of paclitaxel. In the present study, through development of animal models bearing human breast and ovarian xenograft tumors, we evaluated the potential influence of dexamethasone on antitumor activity of paclitaxel in vivo. The results demonstrated that pretreatment of dexamethasone significantly attenuated therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors. The inhibition rate of 20 mg paclitaxel/kg on the growth of breast and ovarian xenograft tumors was around 20-25% less when the animals were pretreated with 1 mg dexamethasone/kg. Further analyses with histological examination and TdT-mediated dUTP nick end labeling assay indicate that pretreatment with dexamethasone clearly interferes with the cytotoxic effects of paclitaxel on both morphological alterations and induction of cell death. Additionally, immunohistochemical staining of proliferation marker Ki-67 indicates that the percentage of proliferating cells in xenograft tumors with pretreatment of dexamethasone is much higher than that in the tumors treated with paclitaxel alone. Put together, the results obtained from the animal experiments show that pretreatment of xenograft tumors with dexamethasone results in significant inhibition of the therapeutic efficacy of paclitaxel in vivo. This finding may have a potential implication on the clinical practice of paclitaxel-based chemotherapy.

Animals↗

PubMed2006

The orexin system regulates alcohol-seeking in rats.

1. Orexin-containing neurons have been implicated in feeding, sleep-wake cycles and more recently in drug-seeking behaviour. 2. Pretreatment of alcohol-preferring (iP) rats with an orexin1 receptor antagonist (SB-334867, 20 mg kg(-1), intraperitoneally) completely abolished an olfactory cue-induced reinstatement of alcohol-seeking behaviour, and also attenuated alcohol responding under an operant fixed ratio regimen without affecting water responding. 3. The mRNA encoding orexin within the hypothalamus was expressed at a similar density in iP and non-preferring (NP) rats; chronic consumption of ethanol in iP rats did not significantly regulate the density of this expression, but did increase the area of expression within the lateral, but not medial, hypothalamus. 4. These data indicate that while orexin may not be implicated in the development of an alcohol preference, re-exposure of cues previously associated with alcohol availability is sufficient and adequate to activate orexin-containing neurons and drive reinstatement of alcohol-seeking.

Alcohol Drinking↗

PubMed2006

Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis.

BACKGROUND: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. METHODS: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. RESULTS: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35-0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82-1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. CONCLUSION: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.

3' Untranslated Regions↗

PubMed2006

Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation.

Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation that causes severe hydronephrosis and obstructive nephropathy in affected mice. The mutation has been mapped to the distal end of mouse chromosome 15, but the mutated gene has not been found. Here, we describe the identification of a single base pair change in aquaporin-2 (Aqp2) in cph mutants through genetic linkage mapping. The C-T change led to the substitution of a Ser (S256) by a Leu in the cytoplasmic tail of the Aqp2 protein, preventing its phosphorylation at S256 and the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct principal cells. The interference with normal trafficking of Aqp2 by this mutation resulted in a severe urine concentration defect. cph homozygotes demonstrated polydipsia and produced a copious amount of hypotonic urine. The urine concentration defect could not be corrected by [deamino-Cys1,D-Arg8]-vasopressin (DDAVP, a vasopressin analog), characteristic of nephrogenic diabetes insipidus. The nephrogenic diabetes insipidus symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery in the mutants before the onset of hydronephrosis suggest that the congenital obstructive nephropathy is most likely a result of the polyuria. This study has revealed the genetic basis for the classical cph mutation and has provided direct genetic evidence that S256 in Aqp2 is indispensable for the apical accumulation, but not the general glycosylation or membrane association, of Aqp2.

Amino Acid Sequence↗

PubMed2006

Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.

For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.

Administration, Oral↗

PubMed2006

Octenyl succinic anhydride modified early indica rice starches differing in amylose content.

Seven early indica rice starches with different amylose contents were modified by octenyl succinic anhydride (OSA) in aqueous suspension systems to evaluate the effect of amylose contents on starch esterification. The crystalline structure and pasting properties of starches were investigated using X-ray diffraction and a Rapid Visco Analyzer (RVA). The results indicated that the amylose content had a positive impact on the OSA modification. As the amylose content increased from 0 to 39.6%, the degree of substitution increased from 0.024 to 0.030 and the reaction efficiency increased from 62.8 to 77.5%. X-ray diffraction scans confirmed that the amylose was mainly present in the amorphous domain of the granule and was highly substituted after the OSA treatment. The RVA profiles demonstrated that the OSA starches had higher viscosities than their native counterparts. Moreover, negative correlations were observed between the amylose content and the major RVA parameters (e.g., peak viscosity, hot paste viscosity, cool paste viscosity, and breakdown viscosity).

Amylose↗

PubMed2006

Effect of methyl jasmonate on secondary metabolites of sweet basil (Ocimum basilicum L.).

The effect of methyl jasmonate (MeJA) in terms of its induction of inherent bioactive chemicals in sweet basil (Ocimum basilicum L.) was evaluated after MeJA was sprayed on healthy basil plants. The total phenolic content of the sweet basil significantly increased after 0.1 and 0.5 mM MeJA treatments compared with the control not subjected to MeJA. Two phenolic compounds, rosmarinic acid (RA) and caffeic acid (CA), were identified as strong antioxidant constituents of the sweet basil. Their amounts also significantly increased after the MeJA treatment. In addition, eugenol and linalool increased 56 and 43%, respectively, by the 0.5 mM MeJA treatment. Due to the accumulation of RA, CA, and eugenol, which possess strong 2,2-diphenyl-1-picrylhydrazyl (DPPH*) free radical scavenging activities, the antioxidant activity of the sweet basil extract was 2.3-fold greater than that of the control after the 0.5 mM MeJA treatment. In the DPPH* assay, the EC50 values of RA, CA, and eugenol were determined as 23, 46, and 59 microM, respectively, which indicated they were 6-, 3-, and 2.4-fold more efficient than BHT (140 microM). Besides, an unidentified HPLC peak in the methanolic extract of the sweet basil was 4.3-fold higher than that of the control after the 0.5 mM MeJA treatment.

Acetates↗

PubMed2006

The pH-dependence of photochemical intermediates of O and P in bacteriorhodopsin by continuous light.

The pH-dependence of the O and P intermediates in the photocycle of bacteriorhodopsin (bR) on the intensity and duration of the exciting flash was investigated for bR glycerol suspensions and bR gelatin films. Green and red laser flashes (532 and 670 nm) were utilized to generate a photoequilibrium state of bR and O at ambient temperature, and UV-vis spectroscopy was used to determine the photoconversion for the bR suspensions and films. The maximal concentration of the O intermediate was observed to be pH-dependent and the dependency was most pronounced at a slightly alkaline pH values. The photochemical conversion from the O to P intermediate was investigated for both bR suspensions and films. The P intermediate was only found in bR gelatin film. These results indicate that bR gelatin film may be an attractive candidate for the information storage based on P intermediate. It is possible, with red light, to create photoproducts which are thermally stable at ambient temperature and that can be photochemically erased.

Bacteriorhodopsins↗

PubMed2006

Liver tumor model with implanted rhabdomyosarcoma in rats: MR imaging, microangiography, and histopathologic analysis.

In compliance with institutional regulations for care and use of laboratory animals, the aim of this study was to establish and characterize a rodent liver tumor model to provide a platform for preclinical assessment of new diagnostic and therapeutic strategies. A rhabdomyosarcoma tumor was implanted in the right and left liver lobes of 20 rats, for a total of 40 tumors. T1- and T2-weighted magnetic resonance (MR) images, diffusion-weighted images, and dynamic susceptibility contrast agent-enhanced perfusion-weighted images were obtained up to 16 days after tumor implantation and were compared with postmortem three-dimensional computed tomographic (CT) images, digital microangiograms, and histopathologic findings. Fifteen tumors were examined with proton ((1)H) MR spectroscopy. All tumors grew, with a mean volume doubling time of 2.2 days +/- 0.9 (standard deviation) and a final size of 591 mm(3)+/- 124. The rhabdomyosarcoma tumor showed hypervascularity at MR imaging, three-dimensional CT, microangiography, and histologic analysis. On dynamic susceptibility contrast-enhanced perfusion-weighted images, the maximum signal intensity decrease differed in time and extent between the tumor and the liver, with a significantly (P < .001) higher relative blood volume, relative blood flow, and permeability value in the tumor than in the liver. With (1)H MR spectroscopy, the rhabdomyosarcoma tumor and the liver featured significant (P < .001) choline and lipid peaks, respectively. Implantation of a rhabdomyosarcoma tumor in the livers of rats is feasible and reproducible, and this animal model seems promising for future testing of new diagnostic and therapeutic strategies.

Angiography↗

PubMed2006

Rac1-null mouse embryonic fibroblasts are motile and respond to platelet-derived growth factor.

Previous studies of Rac1 in fibroblasts have used dominant negative constructs, which may have nonspecific effects. We used a conditional Rac1 allele to critically examine Rac1 function in mouse fibroblasts. Lack of Rac1 had dramatic effects on nonconfluent cells, which were elongated and had extensive blebbing, but no lamellipodia or ruffle formation. However, Rac1-null fibroblasts translocated using pseudopodia-like protrusions without lamellipodia, migrating toward a platelet-derived growth factor (PDGF) gradient as efficiently as their wild-type counterparts. Rac1-null fibroblasts closed wounds in vitro and spread on a fibronectin substrate, although at a slower rate than wild-type cells. However, Rac1-null cells were markedly impaired in proliferation, with a defect in G1 to S transition, although they were capable of surviving in culture for more than 2 wk. These results refine our understanding of the functions of Rac1, indicate that lamellipodia formation is not required for cell motility, and show that PDGF-induced chemotaxis can occur in the absence of both lamellipodia and Rac1.

Actins↗