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Biomedical subjects

Yu Chen

Publications and source records attributed to Yu Chen.

At least 55 records · Page 3Linked to original sources

Variants in estrogen metabolism and biosynthesis genes and urinary estrogen metabolites in women with a family history of breast cancer.

We examined associations between polymorphisms in genes related to estrogen metabolism (CYP1B1 codon 432G --> C rs#1056836, CYP1B1 codon 453A --> G rs#1800440, COMT codon 158G --> A rs#4680) and biosynthesis (CYP17 T --> C promoter rs#743572, CYP19 exon 4 TTTA repeat) and urinary estrogen metabolites (2-hydroxyestrogens (2-OHE), 16alpha-hydroxyestrone (16alpha-OHE1), and their ratio) in a pilot study of 64 pre- and post-menopausal women with a family history of breast cancer. Women were participants in the Metropolitan New York Registry of Breast Cancer Families, one of six international sites of the National Cancer Institute's Breast Cancer Family Registry. We used linear regression to examine the effects of genetic variants on log-transformed urinary estrogen metabolites. After adjusting for menopausal status, BMI, and age, carriers of the CYP1B1 codon 453G variant allele had 31.0% lower levels of 2-OHE (P-value = 0.05) and 40.2% lower levels of 16alpha-OHE1 (P = 0.01). Results were similar after restricting the analyses to pre-menopausal women (n = 41). Consistent with other studies, among pre-menopausal women, carriers of the COMT codon 158A variant allele had increased 2-OHE levels (P = 0.03) and an increased 2-OHE/16alpha-OHE1 ratio (P = 0.04); carriers of the CYP17 C promoter variant allele had increased 2-OHE levels (P = 0.08). To our knowledge this is the first report showing associations between the CYP1B1 codon 453G variant allele and urinary 2-OHE and 16alpha-OHE1 metabolites. Further larger studies should be conducted to confirm these results. Future identification of individuals with genetic polymorphisms that affect estrogen metabolism and biosynthesis may help characterize women at higher breast cancer risk and could guide breast cancer prevention strategies for those individuals.

Adult↗

Effect of intracoronary transplantation of autologous bone marrow-derived mononuclear cells on outcomes of patients with refractory chronic heart failure secondary to ischemic cardiomyopathy.

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p < 0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p < 0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.

Aged↗

Effects of selective estrogen receptor modulator raloxifene plus 17-beta estradiol in aorta and mammary gland of female experimental atherosclerosis rabbits and possible involvement of ERK signal transduction pathway.

The present study investigated the effects of raloxifene, a second generation selective estrogen receptor modulator (SERM), plus 17-betaE2 on aortic atherosclerosis and mammary gland hyperplasia in ovariectomized, cholesterol-fed rabbits. Following 10 weeks of raloxifene, 17-betaE2, or raloxifene plus 17-betaE2 administration, serum total cholesterol, triglyceride, low density lipoprotein were significantly decreased in the drug groups compared to the placebo group. Consistent with serum lipid results, the total lesion area for each aorta of the drug groups decreased significantly as compared to the placebo group. HE staining of aorta paraffin section showed that in the drug groups the endothelial monolayer was almost continuous. While in mammary gland, HE staining of paraffin sections indicated the hyperplasia of epithelial cells (in 17-betaE2 group) was obviously inhibited in raloxifene plus 17-betaE2 group. In cultured vascular smooth muscle cell (VSMC), the results of MTT and [3H]TdR incorporation showed that the drug groups could inhibit AngII-induced proliferation of VSMC. Western blotting proved that raloxifene plus 17-betaE2 inhibited the expression of phosphorylated ERK protein, similar to 17-betaE2 but different from raloxifene. This effect was inhibited by PD98059 (inhibitor of MAPK) or ICI182780 (ER antagonist). In conclusion, this study suggests that SERM raloxifene plus 17-betaE2 improves the lipid metabolism and relieves the aorta changes of female experimental atherosclerosis rabbits, which are partly implemented by the inhibition of VSMC growth through ERK cascade. The hyperplasia of mammary gland epithelial cells could be significantly inhibited by raloxifene plus 17-betaE2.

Animals↗

An iterative refinement algorithm for consistency based multiple structural alignment methods.

MOTIVATION: Multiple STructural Alignment (MSTA) provides valuable information for solving problems such as fold recognition. The consistency-based approach tries to find conflict-free subsets of alignments from a pre-computed all-to-all Pairwise Alignment Library (PAL). If large proportions of conflicts exist in the library, consistency can be hard to get. On the other hand, multiple structural superposition has been used in many MSTA methods to refine alignments. However, multiple structural superposition is dependent on alignments, and a superposition generated based on erroneous alignments is not guaranteed to be the optimal superposition. Correcting errors after making errors is not as good as avoiding errors from the beginning. Hence it is important to refine the pairwise library to reduce the number of conflicts before any consistency-based assembly. RESULTS: We present an algorithm, Iterative Refinement of Induced Structural alignment (IRIS), to refine the PAL. A new measurement for the consistency of a library is also proposed. Experiments show that our algorithm can greatly improve T-COFFEE performance for less consistent pairwise alignment libraries. The final multiple alignment outperforms most state-of-the-art MSTA algorithms at assembling 15 transglycosidases. Results on three other benchmarks showed that the algorithm consistently improves multiple alignment performance. AVAILABILITY: The C++ code of the algorithm is available upon request.

Algorithms↗

Collective reaction behavior of an oscillating system coupled with an excitable reaction.

The collective reaction behavior of limit cycles coupled to a nonoscillatory forcing is investigated experimentally and computationally. The coupled chemical system is constructed by adding 1,4-cyclohexanedione (CHD), a species which is capable of forming an oscillator with acidic bromate, into the cerium-catalyzed Belousov-Zhabotinsky reaction. Two levels of coupling exist in the system: (1) through autocatalytic reactions with bromine dioxide radicals and (2) via reactions with oxidized metal catalysts. Experiments illustrate that there is an optimum [1,4-CHD]/[cerium] ratio for inducing complex oscillations, whereas in the 1,4-CHD and malonic acid concentration phase plane two resonant ratios are observed for the onset of complex behavior. In addition, bromate, the oxidant for both suboscillators, also exhibits subtle influences on the complexity of the collective reaction behavior. The experimental observations are qualitatively reproduced with the Field-Koros-Noyes mechanism, modified to account for the coupling reactions with the 1,4-CHD-bromate system.

Journal Article↗

Blood arsenic as a biomarker of arsenic exposure: results from a prospective study.

Exposure to arsenic (As)-contaminated drinking water affects millions of people worldwide. Arsenic exposure is associated with skin lesions, skin, lung, kidney and liver cancers, neurologic and cardiovascular effects. Past studies involving biomarkers of As exposure have typically examined urinary As (UAs) (adjusted for urinary creatinine), hair or toenail As, but not blood As (BAs) since blood concentrations are exceedingly low and are not detectable by conventional atomic absorption spectrophotometric techniques. In a case-cohort analysis of 303 newly diagnosed cases of skin lesions, and 849 subcohort members randomly selected from 8092 participants in the health effects of as longitudinal study (HEALS) in Araihazar, Bangladesh, we measured blood, urine and water As concentrations, and examined their associations with each other, and with the risk for skin lesions. BAs concentrations were highly correlated with creatinine-adjusted UAs concentrations (r=0.85) and with water As (WAs) (r=0.75). We observed consistent dose-response relationships between the risk of skin lesions and all the measures of As exposure. Rate ratios (RRs) for skin lesions by quintile of As exposure, adjusted for age and gender, revealed that the two highest quintiles were significantly related to an increased risk of skin lesions for each measure of exposure: BAs, UAs, WAs and a time-weighted water As variable. This prospective study confirms the increased risk of skin lesions in relation to As concentrations in blood, urine and water and also establishes that BAs is a useful biomarker of As exposure in this study population.

Adult↗

Structure of stem-loop IV of Tetrahymena telomerase RNA.

Conserved domains within the RNA component of telomerase provide the template for reverse transcription, recruit protein components to the holoenzyme and are required for enzymatic activity. Among the functionally essential domains in ciliate telomerase RNA is stem-loop IV, which strongly stimulates telomerase activity and processivity even when provided in trans. The NMR structure of Tetrahymena thermophila stem-loop IV shows a highly structured distal stem-loop linked to a conformationally flexible template-proximal region by a bulge that severely kinks the entire RNA. Through extensive structure-function studies, we identify residues that contribute to both these structural features and to enzymatic activity, with no apparent effect on the binding of TERT protein. We propose that the bending induced by the GA bulge and the flexibility of the template-proximal region allow positioning of the prestructured apical loop during the catalytic cycle.

Animals↗

Study of a new type linear ultrasonic motor with double-driving feet.

A new type linear USM with double-driving feet has been developed. The stator consists of eight piezoelectric ceramic plates and one brass plate. Piezoelectric ceramics plates are polarized along the thickness and are symmetrically bonded to the two surfaces of one rectangle brass plate. Double-driving feet are assembled on the same side of the brass plate. The working vibration mode is a composite in-plane bimode, which consists of the first longitudinal in-plane vibration mode and the second bending one. The basic size of the linear USM is determined carefully by FEA. The characteristics of the prototype motor were measured experimentally.

Journal Article↗

Comparison of the results for three automated immunoassay systems in determining serum HBV markers.

BACKGROUND: Automated immunoassay analyzers are used to identify hepatitis B virus (HBV) serum markers. In regions with high prevalence of HBV, it is imperative to compare test results from different immunoassay analyzers. METHODS: Samples from 496 subjects were collected and HBV markers were determined (double-blind, parallel manner) using Abbott AxSYM, Roche Modular Analytics E170, and Abbott Architect i2000). RESULTS: Concurrence between AxSYM and E170 was 97.78% for HBsAg, 91.13% for anti-HBs, 98.79% for anti-HBc, 98.39% for HBeAg, and 88.91% for anti-HBe. Positive rates of anti-HBs and anti-HBe from AxSYM were lower than E170 (P<0.01). Concurrence between AxSYM and Architect i2000 was 98.79% for HBsAg, 91.33% for anti-HBs, 95.97% for anti-HBc, 98.39% for HBeAg, and 95.77% for anti-HBe. Positive anti-HBs rates from AxSYM were lower than Architect i2000 (P<0.01). Concurrence between E170 and Architect i2000 was 97.38% for HBsAg, 94.15% for anti-HBs, 95.56% for anti-HBc, 99.60% for HBeAg, and 88.10% for anti-HBe. Positive anti-HBe rates using Architect i2000 were lower than E170 (P<0.01). Overall, the greatest differences were observed in samples with low-level serum HBV markers. CONCLUSION: Significant discrepancies were observed among results for the 3 automated immunoassay analyzers, especially for low-level anti-HBs and anti-HBe results.

Adolescent↗

The role of brinker in eggshell patterning.

Drosophila oogenesis provides a useful system to study signal transduction pathways and their interactions. Through clonal analysis, we found that brinker (brk), a repressor of Dpp signaling, plays an important role in the Drosophila ovary, where its function is essential for dorsal appendage formation. In the absence of brk, operculum fates are specified at the expense of dorsal appendage fates. Brk is expressed by most of the oocyte associated follicle cells, starting from stage 8 of oogenesis. Transforming Growth Factor beta (TGFbeta) signaling represses brk expression in both the early stage egg chambers and in the anterior follicle cells. In brk mutant follicle cell clones at the dorsal anterior region, Broad Complex (BR-C) expression is down-regulated in a larger domain than in wild type. We show that BR-C is required for dorsal appendage development. In large anterior BR-C mutant clones, dorsal appendages are absent, and instead, the eggshell has an enlarged operculum like region at the anterior. In addition, we show that the Epidermal Growth Factor (EGF) receptor signaling represses the TGFbeta signaling in oogenesis by up-regulating brk expression. From our results and previously published data, it appears that anterior follicle cells integrate the levels of EGF receptor activation and TGFbeta receptor activation. Operculum fate results when the sum of the level of activation of both pathways reaches a threshold level, and reduction of activity of one pathway can be compensated to some extent by increase in the other pathway.

Animals↗

Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells.

Embryonic stem cells (ESCs) overexpressing the vascular endothelial growth factor (VEGF) improve cardiac function in mouse models of myocardial ischemia and infarction by mechanisms that are poorly understood. Here we studied the effects of VEGF on cardiomyocyte differentiation of mouse ESCs in vitro. We used flow cytometry to determine the expression of alpha-myosin heavy chain (alpha-MHC), cardiac troponin I (cTn-I), and Nkx2.5 in differentiated ESCs. VEGF (20 ng/ml) significantly enhanced alpha-MHC, cTn-I, and Nkx2.5 expression in differentiated ESCs. Western blot analysis confirmed these findings. We found that VEGF receptor FMS-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1) expression increased during ESC differentiation. Antibodies against Flk-1 totally blocked and against Flt-1 partially blocked VEGF-induced NKx2.5-positive-stained cells. The ERK inhibitor PD-098059 abolished VEGF-induced cardiomyocyte differentiation of ESCs. Our results suggest that VEGF promotes cardiomyocyte differentiation predominantly by ERK-mediated Flk-1 activation and, to a lesser extent, by Flt-1 activation. These findings may be of significance for stem cell and growth factor therapies to regenerate failing cardiomyocytes.

Animals↗

Arsenic exposure from drinking water and risk of premalignant skin lesions in Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal Study.

Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.

Adult↗

[The biomechanical study of craniovertebral junction fixation with posterior transarticular screw].

OBJECTIVE: To evaluate the stability of biomechanics of occipitoatlantoaxial reconstruction with transarticular screw fixation. METHODS: Twelve fresh human cadaveric occipitocervical spine specimens were mounted in a custom-designed, spine-testing machine that applied pure moments while recording the three-dimensional angular movement at occiput (Oc)-C(1) and C(1 - 2) segments. The specimens were tested under seven different conditions: the intact (intact group), the occipitoatlantoaxial instability (Destabilized group), fixation with Ti-cable plus bone graft group (cable + graf group), fixation with the transarticular fixation (CTS group), fixation with SUMMIT occitocervical spinal fixation system (SUMMIT group), fixation with transarticular screw plus bone graft (CTS + graf group), and fixation with SMMIT system and plus graft group (SUMMIT + graf group). The data obtained were statistically analyzed. RESULTS: The CTS group reduced motion to well within the normal rang. In the Oc-C(1) segment, The CTS group and SUMMIT group allowed a very small rang of motion (ROM) and neutral zone (NZ) during lateral bending and axial rotation. The ROM and NZ during flexion and extension of the SUMMIT group, were significantly smaller than those of cable + graf group and CTS group (6.64 degrees +/- 0.59 degrees, 2.49 degrees +/- 0.26 degrees, 0.50 degrees +/- 0.03 degrees, 0.21 degrees +/- 0.01 degrees, 0.27 degrees +/- 0.07 degrees, 0.13 degrees +/- 0.01 degrees vs 10.01 degrees +/- 1.26 degrees, 3.80 degrees +/- 0.79 degrees, 7.93 degrees +/- 1.34 degrees, 3.18 degrees +/- 0.95 degrees, 9.54 degrees +/- 0.87 degrees, 5.93 degrees +/- 0.74 degrees, P < 0.05). In the C(1 - 2) segment, ROM and NZ in all directions of CTS group were smaller in rotation than SUMMIT group (1.64 degrees +/- 0.39 degrees, 0.61 degrees +/- 0.15 degrees, 0.14 degrees +/- 0.05 degrees, 0.02 degrees +/- 0.01 degrees, 0.32 degrees +/- 0.04 degrees, 0.08 degrees +/- 0.01 degrees, vs 0.21 degrees +/- 0.04 degrees, 0.07 degrees +/- 0.03 degrees, 0.21 degrees +/- 0.12 degrees, 0.10 degrees +/- 0.02 degrees, 2.92 degrees +/- 0.28 degrees, 1.27 degrees +/- 0.11 degrees, all P < 0.05). There was no significant difference in ROM and NZ in all directions between CTS + graf group and SUMMIT + Graf group (P > 0.05). CONCLUSION: In vivo biomechanics studies show that posterior occipitocervical transarticular fixation has unique features in reconstructing dynamic stability of the occipitoatlantoaxis, especially in controlling stability of rotation and lateral flexion, thus ensuring successful fusion of the implanted bone and allowing for clinical use of the technique.

Adult↗

Mechanisms underlying long- and short-range nodal signaling in Zebrafish.

Precise regulation of the signaling range of secreted molecules is essential for proper pattern formation during development. The Nodal family of TGF-beta proteins has been shown to function as both short- and long-range signals. But the underlying mechanisms remain elusive. In this study, we investigated the regulation of the signaling range of zebrafish Nodal proteins Cyclops and Squint, which are short- and long-range signals, respectively. We show that (1) the stability of Cyclops and Squint correlates with the activity range but increasing the stability of the short-range Cyclops does not increase its signaling range; (2) structural differences in the N-terminus region of the mature peptides of Cyclops and Squint determine their differences in the signaling range and swapping the N-terminus region of the Squint mature ligand into that of Cyclops makes the latter function at a distance.

Amino Acid Sequence↗

Sintering of passivated gold nanoparticles under the electron beam.

Time-lapse studies of a film of passivated gold nanoparticles under electron beam irradiation have been performed using a transmission electron microscope, revealing the microscopic dynamics of the sintering process at the single nanoparticle level. It is found that the sintering of individual passivated gold nanoparticles under electron irradiation is local and mainly depends on the sensitivity of the passivating ligands to the electron beam. A multilayer film is less stable than monolayer film, consistent with the enhanced generation of secondary electrons. The observations also reveal a significant difference between the sintering of passivated nanoparticles and bare metal particles, especially regarding the size effect on the sintering rate. The formation of a neck between adjacent nanoparticles further indicates a mechanism driven by surface diffusion rather than Ostwald ripening at the initial sintering stage.

Journal Article↗

Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents.

Current treatments for chronic hepatitis B virus (HBV) infection include the use of interferon-alpha and of nucleoside analogs lamivudine, adefovir and entecavir. However, the use of interferon-alpha has many side effects while that of nucleosidic inhibitors can lead to the emergence of resistant viruses. Hence, new drugs for the treatment of HBV infection are still highly desired. Oxadiazoles have been observed to exhibit antiviral activities against RNA viruses. In this study, a facile synthesis of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles is reported. The compounds were then evaluated for their anti-HBV activity. 1-[2-[5-(1-Benzenesulfonyl-propyl)-[1,3,4]oxadiazol-2-yl-sulfanyl]-ethyl]-4-(2-methoxy-phenyl)-piperazine (1i) was able to inhibit the expression of the viral antigens, HBsAg and HBeAg in a concentration-dependent manner with no cytotoxic effects and without any effects on the expression of viral transcripts. Concentration- and time-dependent reductions in virion production were also observed. The inhibition of virion production was comparable to that of lamivudine and EC(50) values of 1.63 and 2.96 microM were obtained for compound 1i and lamivudine, respectively. Thus, in addition to the antiviral effects on RNA viruses, oxadiazoles also have anti-HBV activities.

Antiviral Agents↗

The deacylation mechanism of AmpC beta-lactamase at ultrahigh resolution.

Beta-lactamases confer bacterial resistance to beta-lactam antibiotics, such as penicillins. The characteristic class C beta-lactamase AmpC catalyzes the reaction with several key residues including Ser64, Tyr150, and Lys67. Here, we describe a 1.07 A X-ray crystallographic structure of AmpC beta-lactamase in complex with a boronic acid deacylation transition-state analogue. The high quality of the electron density map allows the determination of many proton positions. The proton on the Tyr150 hydroxyl group is clearly visible and is donated to the boronic oxygen mimicking the deacylation water. Meanwhile, Lys67 hydrogen bonds with Ser64Ogamma, Asn152Odelta1, and the backbone oxygen of Ala220. This suggests that this residue is positively charged and has relinquished the hydrogen bond with Tyr150 observed in acyl-enzyme complex structures. Together with previous biochemical and NMR studies, these observations indicate that Tyr150 is protonated throughout the reaction coordinate, disfavoring mechanisms that involve a stable tyrosinate as the general base for deacylation. Rather, the hydroxyl of Tyr150 appears to be well positioned to electrostatically stabilize the negative charge buildup in the tetrahedral high-energy intermediate. This structure, in itself, appears consistent with a mechanism involving either Tyr150 acting as a transient catalytic base in conjunction with a neutral Lys67 or the lactam nitrogen as the general base. Whereas mutagenesis studies suggest that Lys67 may be replaced by an arginine, disfavoring the conjugate base mechanism, distinguishing between these two hypotheses may ultimately depend on direct determination of the pK(a) of Lys67 along the reaction coordinate.

Acylation↗

Crosslinked carboxymethylchitosan-g-poly(acrylic acid) copolymer as a novel superabsorbent polymer.

A novel carboxymethylchitosan-g-poly(acrylic acid) (CMCTS-g-PAA) superabsorbent polymer was prepared through graft polymerization of acrylic acid onto the chain of carboxymethylchitosan and subsequent crosslinking. It was demonstrated by FTIR spectroscopy that acrylic acid had been graft polymerized with carboxymethylchitosan. The thermal stability of the polymer was characterized by thermogravimetric analysis. By studying the swelling ratio of the polymer synthesized under different conditions, optimization conditions were found for a polymer with the highest swelling ratio. The rate of water absorption of the polymer was high, and the swelling of the polymer fitted the process of first dynamics. The swelling ratio of the polymer was pH-dependent.

Absorption↗