Biomedical subjects

Quan Chen

Publications and source records attributed to Quan Chen.

At least 19 recordsLinked to original sources

PubMed2026

Leveraging environmental applications and risks of coal gangue: A critical review on authigenic inorganic heavy metals, organic contaminants, and the removal of exogenetic contaminants.

Coal gangue (CG) as bulk solid waste has seriously threatened the ecosystem. Therefore, identifying the key risk drivers and exploring feasible disposal methods for CG are essential for developing a sustainable strategy. However, there is currently a lack of comprehensive information that balances the contamination risks with the valuable constituents present in CG, which hinders its full potential for sustainable use without negative environmental impacts. Given the complex composition and associated risks, we propose that addressing the critical properties related to contamination is crucial for the efficient utilization of CG. On this premise, we summarized several practical resource pathways (ecological multifunctional materials, extraction of rare elements, and soil additives) that are more favorable for sustainable development relative to conventional disposals. Meanwhile, we also propose that coupling disposals could intensely reduce CG's environmental footprints and capital costs. Consequently, regardless of the number of challenges to be solved, we believe the CG has broad application prospects, and we hope this review will promote the conversion of CG into an asset with lower ecological and social impacts.

Metals, Heavy↗

PubMed2006

Recombinant M. smegmatis vaccine targeted delivering IL-12/GLS into macrophages can induce specific cellular immunity against M. tuberculosis in BALB/c mice.

In the present study, we constructed a viable therapeutic vaccine of recombinant M. smegmatis mediated IL-12/GLS (granulysin) gene transfer into murine macrophages to exert the immunotherapy effects on the Mycobacterium tuberculosis infection. We tested this recombinant therapeutic vaccine in an in vivo study to determine its capability of stimulating host specific immune responses against M. tuberculosis. BALB/c mice intranasally immunized with the therapeutic vaccine developed an efficient Th1 protective immune response against M. tuberculosis which was equal to that of the BCG strain. Inoculation intranasally with this viable vaccine induced high level of serum IFN-gamma, IL-12 and IgG2a. The viable vaccine was capable of inducing purified protein derivative (PPD) antigen-specific splenocytes proliferation and IFN-gamma production from T cells in spleens of the immunized mice. In addition, intranasally inoculation with the viable vaccine can induce PPD antigen-specific sIgA production in the broncho-alveolar lavage fluid (BALF) of the immunized mice. No change of IL-4 level was found in all groups. The therapeutic mechanism of this viable vaccine against M. tuberculosis infection observed here appeared to be a result of the specific Th1 immune response activated by mycobacterium antigen from M. smegmatis and the expression of sIL-12/GLS in alveolar macrophages via the M. smegmatis-mediated gene transfer method. This research demonstrates that the therapeutic gene can be introduced into a host by viable mycobacteria works to induce the host specific immune response against M. tuberculosis infection in vivo. Since this therapeutic vaccine can strongly induce specific Th1 responses against M. tuberculosis in BALB/c mice and has no obviously harmfulness to the host simultaneously, the recombinant vaccine might be a potential candidate therapeutic vaccine against tuberculosis.

Animals↗

PubMed2006

Identification of genes regulated by Wnt/beta-catenin pathway and involved in apoptosis via microarray analysis.

BACKGROUND: Wnt/beta-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/beta-catenin pathway modification of the cellular apoptosis. METHODS: To identify potential genes regulated by Wnt/beta-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of beta-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR. RESULTS: Stably integrated inducible RNAi vector could effectively suppress beta-catenin expression and the transcriptional activity of beta-catenin/TCF. Meanwhile, depletion of beta-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-kappaB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of beta-catenin. CONCLUSION: Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/beta-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified beta-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.

Apoptosis↗

PubMed2006

Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2.

Cells without Bak and Bax are largely resistant to apoptosis, despite the presence of other key components of the apoptotic machinery. We screened 7,800 natural compounds and found several that could specifically induce caspase activation and the release of cytochrome c (cyto c) in the bak(-/-)/bax(-/-) cells. One of these was gossypol, a polyphenolic compound naturally found in cottonseed that has been used in antifertility trials. We found that gossypol, but not other Bcl-2-interacting molecules, induced cyto c release and loss of mitochondrial membrane potential (delta psi m) independently of mPTP and Bak/Bax activation. Furthermore, we found that gossypol induced an allosteric change in Bcl-2 in both bak(-/-)/bax(-/-) cells and Bcl-2 overexpressing cells. This change in Bcl-2 conformation led to the release of cyto c in the presence of Bcl-2 and Bcl-xL in reconstituted proteoliposomes. We also observed that gossypol substantially reduced the growth of tumor xenografts from Bcl-2 overexpressing cells in nude mice. We conclude that gossypol converts the antiapoptotic molecule Bcl-2 into a proapoptotic molecule that can mediate the release of cyto c and induce apoptosis.

Animals↗

PubMed2006

Real-time respiration monitoring using the radiotherapy treatment beam and four-dimensional computed tomography (4DCT)--a conceptual study.

Real-time knowledge of intra-fraction motion, such as respiration, is essential for four-dimensional (4D) radiotherapy. Surrogate-based and internal-fiducial-based methods may suffer from one or many drawbacks such as false correlation, being invasive, delivering extra patient radiation, and requiring complicated hardware and software development and implementation. In this paper we develop a simple non-surrogate, non-invasive method to monitor respiratory motion during radiotherapy treatments in real time. This method directly utilizes the treatment beam and thus imposes no additional radiation to the patient. The method requires a pre-treatment 4DCT and a real-time detector system. The method combines off-line processes with on-line processes. The off-line processes include 4DCT imaging and pre-calculating detector signals at each phase of the 4DCT based on the planned fluence map and the detector response function. The on-line processes include measuring detector signal from the treatment beam, and correlating the measured detector signal with the pre-calculated signals. The respiration phase is determined as the position of peak correlation. We tested our method with extensive simulations based on a TomoTherapy machine and a 4DCT of a lung cancer patient. Three types of simulations were implemented to mimic the clinical situations. Each type of simulation used three different TomoTherapy delivery sinograms, each with 800 to 1000 projections, as input fluences. Three arbitrary breathing patterns were simulated and two dose levels, 2 Gy/fraction and 2 cGy/fraction, were used for simulations to study the robustness of this method against detector quantum noise. The algorithm was used to determine the breathing phases and this result was compared with the simulated breathing patterns. For the 2 Gy/fraction simulations, the respiration phases were accurately determined within one phase error in real time for most projections of the treatment, except for a few projections at the start and end of the treatment in which beam intensities were extremely low. At 2 cGy/fraction dose level, the method can still determine the respiration phase very well with less than 10% of projections having more than two phases (approximately 1 s) error. This technique can also be applied in other delivery systems such as orthogonal x-ray systems, although in those cases it would entail the delivery of additional non-treatment radiation.

Algorithms↗

PubMed2006

Deformable registration of the planning image (kVCT) and the daily images (MVCT) for adaptive radiation therapy.

The incorporation of daily images into the radiotherapy process leads to adaptive radiation therapy (ART), in which the treatment is evaluated periodically and the plan is adaptively modified for the remaining course of radiotherapy. Deformable registration between the planning image and the daily images is a key component of ART. In this paper, we report our researches on deformable registration between the planning kVCT and the daily MVCT image sets. The method is based on a fast intensity-based free-form deformable registration technique. Considering the noise and contrast resolution differences between the kVCT and the MVCT, an 'edge-preserving smoothing' is applied to the MVCT image prior to the deformable registration process. We retrospectively studied daily MVCT images from commercial TomoTherapy machines from different clinical centers. The data set includes five head-neck cases, one pelvis case, two lung cases and one prostate case. Each case has one kVCT image and 20-40 MVCT images. We registered the MVCT images with their corresponding kVCT image. The similarity measures and visual inspections of contour matches by physicians validated this technique. The applications of deformable registration in ART, including 'deformable dose accumulation', 'automatic re-contouring' and 'tumour growth/regression evaluation' throughout the course of radiotherapy are also studied.

Algorithms↗

PubMed2006

Nitric oxide signaling in stretch-induced apoptosis of neonatal rat cardiomyocytes.

Pressure overload associated with hypertension is an important pathological factor leading to heart remodeling and ultimately heart failure partially due to cardiomyocyte apoptosis. Here we show that endogenous NO signaling plays a critical role in mechanical stretch-induced cardiomyocyte apoptosis. Mechanical stretch induced elevated expression of both eNOS and inducible NO synthase (iNOS) and increased synthesis of NO. A sustained increase in iNOS expression was also found in hearts of hypertensive rats in vivo. Blockade of NO signaling by inhibitors of NOS (L-NAME and AMT) or downstream guanylyl cyclase (ODQ) strongly inhibited stretch-induced apoptosis, mitochondria depolarization, and cytochrome c release, suggesting that NO is required in stretch-induced cardiomyocyte apoptosis. The expression of iNOS, but not eNOS, was blocked by L-NAME and ODQ, indicating that the iNOS induction is NO dependent. The initial elevation of NO is likely due to Ca(2+)-dependent activation of eNOS because elimination of intracellular calcium by EGTA-AM inhibited both iNOS induction and NO elevation. Other calcium signaling inhibitors (nifedipine, ryanodine, thapsigargin, and ionic gadolinium) also attenuated the initial NO elevation. These data indicate that mechanical signals initiate Ca(2+)-dependent NO synthesis, which is further amplified by activation of NO-induced iNOS expression, to regulate cardiomyocyte apoptosis.

Animals↗

PubMed2006

Comparative isoschizomer profiling of cytosine methylation: the HELP assay.

The distribution of cytosine methylation in 6.2 Mb of the mouse genome was tested using cohybridization of genomic representations from a methylation-sensitive restriction enzyme and its methylation-insensitive isoschizomer. This assay, termed HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR), allows both intragenomic profiling and intergenomic comparisons of cytosine methylation. The intragenomic profile shows most of the genome to be contiguous methylated sequence with occasional clusters of hypomethylated loci, usually but not exclusively at promoters and CpG islands. Intergenomic comparison found marked differences in cytosine methylation between spermatogenic and brain cells, identifying 223 new candidate tissue-specific differentially methylated regions (T-DMRs). Bisulfite pyrosequencing confirmed the four candidates tested to be T-DMRs, while quantitative RT-PCR for two genes with T-DMRs located at their promoters showed the HELP data to be correlated with gene activity at these loci. The HELP assay is robust, quantitative, and accurate and is providing new insights into the distribution and dynamic nature of cytosine methylation in the genome.

Animals↗

PubMed2006

Automatic re-contouring in 4D radiotherapy.

Delineating regions of interest (ROIs) on each phase of four-dimensional (4D) computed tomography (CT) images is an essential step for 4D radiotherapy. The requirement of manual phase-by-phase contouring prohibits the routine use of 4D radiotherapy. This paper develops an automatic re-contouring algorithm that combines techniques of deformable registration and surface construction. ROIs are manually contoured slice-by-slice in the reference phase image. A reference surface is constructed based on these reference contours using a triangulated surface construction technique. The deformable registration technique provides the voxel-to-voxel mapping between the reference phase and the test phase. The vertices of the reference surface are displaced in accordance with the deformation map, resulting in a deformed surface. The new contours are reconstructed by cutting the deformed surface slice-by-slice along the transversal, sagittal or coronal direction. Since both the inputs and outputs of our automatic re-contouring algorithm are contours, it is relatively easy to cope with any treatment planning system. We tested our automatic re-contouring algorithm using a deformable phantom and 4D CT images of six lung cancer patients. The proposed algorithm is validated by visual inspections and quantitative comparisons of the automatic re-contours with both the gold standard segmentations and the manual contours. Based on the automatic delineated ROIs, changes of tumour and sensitive structures during respiration are quantitatively analysed. This algorithm could also be used to re-contour daily images for treatment evaluation and adaptive radiotherapy.

Aged↗

PubMed2006

Attenuation estimations using envelope echo data: analysis and simulations.

Previously we described a video signal analysis (VSA) method for measuring backscatter and attenuation from B-Mode image data. VSA computes depth-dependent ratios of the mean echo intensity from a sample to the mean echo intensity from a reference phantom imaged using identical scanner settings. The slope of a line-fit of this ratio (expressed in dB) versus depth is related to the attenuation of the sample. This paper investigates conditions for which the echo intensity ratio versus depth is independent of transducer pulsing characteristics and instrument settings, and depends only on the properties of the sample and the reference. A theoretical model is described for the echo signal power versus depth from a uniform medium containing scatterers. The model incorporates bandwidth, frequency and media attenuation. Results show that the sample-to-reference echo intensity ratio versus depth is a curve, the departure of which from a straight line is a function of the relative attenuation of the two media, the imaging system bandwidth and the initial frequency. The model also leads to a depth-dependent "effective frequency" determination in the VSA method. Model predictions are verified using RF signals computed by an acoustic pulse-echo simulation program.

Computer Simulation↗

PubMed2006

The Ultrasonix 500RP: a commercial ultrasound research interface.

Unlike researchers in magnetic resonance imaging who have considerable access to high level tools and to data at a very basic level on their scanners, those involved with ultrasound have found little in the way of meaningful and widespread access to even the most basic echo signals in their clinical systems. Interest has emerged, however, in ultrasound research interfaces on commercial scanners to provide access to raw ultrasound data and control of basic research functions. This paper describes initial experience gained on one such ultrasound system. The Ultrasonix 500RP system provides research access to the data at multiple points in the signal processing chain and allows control over most imaging parameters. The Ultrasonix system allows for three methods of research control. One is implemented along with the standard clinical imaging software using "mouseover" screens on the periphery of the application window. These screens are configured by the user to display various signal processing variables, which can be modified in real time. Second, the system can be controlled via a user-written remote control client application interacting through the clinical exam software. Lastly, the user can write a complete application which initializes the basic ultrasound module but need not use the Ultrasonix clinical exam software. All of the modes can be done locally on the scanner itself or via a network, and are based on software developed in C++ with libraries supplied with the scanner. Two examples are presented in this paper from the evaluation of the system in "real world" applications. Measurements of absolute backscatter coefficients and attenuation coefficients versus frequency are shown and elastograms utilizing spatial compounding are described.

Biomedical Research↗

PubMed2006

Spatial-angular compounding for elastography using beam steering on linear array transducers.

Spatial-angular compounding is a new technique that enables the reduction of noise artifacts in ultrasound elastography. Under this method, compounded elastograms are obtained from a spatially weighted average of local strain estimated from radio frequency (rf) echo signals acquired at different insonification angles. In previous work, the acquisition of the rf signals was performed through the lateral translation of a phased-array transducer. Clinical applications of angular compounding would, however, require the utilization of beam steering on linear-array transducers to obtain angular data sets, which is more efficient than translating phased-array transducers. In this article, we investigate the performance of angular compounding for elastography by using beam steering on a linear-array transducer. Quantitative experimental results demonstrate that spatial angular compounding provides significant improvement in both the elastographic signal-to-noise ratio and the contrast-to-noise ratio. For the linear array transducer used in this study, the optimum angular increment is around 1.5 degrees-3.75 degrees, and the maximum angle that can be used in angular compounding should not exceed 10 degrees.

Artifacts↗

PubMed2006

Initial clinical experience imaging scatterer size and strain in thyroid nodules.

OBJECTIVE: This article describes a new research ultrasound scanner that can be programmed to produce elastograms and backscatter parametric images in real time. Its performance was evaluated in a clinical setting. METHODS: Radio frequency data were acquired from 13 patients with thyroid nodules and from 4 normal thyroids, along with reference phantom data. Scatterer size was deduced by measuring the backscatter versus frequency and fitting data to a model. Strain was obtained by a cross-correlation method, comparing precompression and postcompression radio frequency signals. Scatterer size contrast was defined as the observed contrast between the "normal" and "abnormal" tissue in the same gland or, when considering diffuse conditions, by comparing with normal values. Strain contrast was estimated if abnormal and normal tissue was captured in the same palpation, that is, excluding diffuse disease, which was the case for 9 subjects. RESULTS: On scatterer size images, 4 nodules exhibited positive contrast versus the adjacent normal parenchyma, indicating larger scatterers. Five nodules were isoechoic, and 4 had negative contrast. Four nodules exhibited positive strain contrast, indicating that they were softer than the normal parenchyma. Two nodules had the same brightness, and 3 were darker than the background thyroid tissue on strain images. CONCLUSIONS: Contrast was observed between nodules and thyroid parenchymal tissue for both types of parametric images. Further work is needed to determine whether the diagnostic importance of these parameters in characterizing thyroid nodules might be worthwhile. Both modes must be of a sufficient frame rate to provide real-time feedback to operators, which will require further work.

Adult↗

PubMed2005

Measurement of rock-core capillary pressure curves using a single-speed centrifuge and one-dimensional magnetic-resonance imaging.

Capillary pressure curves are widely used in materials, soil, and environmental sciences, and especially in the petroleum industry. The traditional (Hassler-Brunner) interpretation of centrifugal capillary pressure data is based on several assumptions. These assumptions are known to lead to significant errors in the measurement of capillary pressure curves. In this work, we propose a new "single-shot" method to measure the capillary pressure curve of a long sedimentary rock core using a single-speed centrifuge experiment and magnetic-resonance imaging to directly determine the water saturation distribution along the length of the sample. Since only a single moderate centrifuge speed is employed, the effect of gravity can be ignored and the outlet boundary condition of the core plug was maintained. The capillary pressure curve obtained by the single-shot method is remarkably consistent with results determined with conventional mercury-intrusion methods. The proposed method is much faster and more precise than traditional centrifuge methods.

Journal Article↗

PubMed2005

Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells.

This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As(2)O(3))-induced apoptosis. We showed that As(2)O(3) treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As(2)O(3). Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As(2)O(3)-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As(2)O(3) were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As(2)O(3) seemed to require stress-induced intracellular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As(2)O(3) might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated.

Annexin A5↗

PubMed2005

Involvement of death receptor signaling in mechanical stretch-induced cardiomyocyte apoptosis.

Recent evidences suggest that mechanical overload associated with abnormal blood pressure causes apoptosis in cardiovascular system. Still, the intracellular signaling leading to cardiomyocyte apoptosis has not been fully defined. Previous reports ascribed stretch-induced cardiomyocyte apoptosis to rennin-angiotensin-system (RAS) signaling and/or mitochondria-dependent apoptosis pathway. The present study shows the involvement of death receptor signaling in mechanical stretch-induced cardiomyocyte apoptosis. By employing a well-described in vitro stretch model, we studied stretch-induced apoptosis and found that the death receptor-mediated apoptotic signaling was activated in stretch-induced apoptosis in neonatal rat cardiomyocytes. The major finding are as following: (1) The mechanical stretch activated death receptor-mediated apoptotic signaling in cardiomyocytes, including activation of caspases 8, 9 and 3, up-regulation of Fas, FasL expression and cell surface trafficking of death ligands (FasL and TRAIL); (2) That exogenous death ligand (TRAIL) enhanced, while soluble death receptor (sDR5) neutralized, stretch-induced apoptosis; (3) Adenovirus-delivered dominant negative FADD (FADD-DN) significantly reduced apoptosis, caspases 8, 9, and 3 activation, and stretch-induced cyt c release from mitochondria. These data clearly suggested mechanical stretch activated death receptor-mediated apoptotic signaling in cardiomyocytes. In conclusion, our data suggest that the FADD-linked death receptor signaling may contribute to stretch-induced cardiomyocyte apoptosis, probably through activating mitochondria-dependent apoptotic signaling.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Disruption of Smad5 gene induces mitochondria-dependent apoptosis in cardiomyocytes.

Our previous studies have shown that SMAD5, an important intracellular mediator of transforming growth factor beta (TGF-beta) family, is required for normal development of the cardiovascular system in vivo. In the current study, we reported that the lack of the Smad5 gene resulted in apoptosis of cardiac myocytes in vivo. To further investigate the mechanism of the Smad5 gene in cardiomyocyte apoptosis, the embryonic stem (ES) cell differentiation system was employed. We found that the myotubes that differentiated from the homozygous Smad5ex6/ex6 mutant ES cells underwent collapse and degeneration during the late stages of in vitro differentiation, mimicking the in vivo observation. By electron microscopy, abnormal swollen mitochondria were observed in cardiomyocytes both from Smad5-deficient embryos and from ES-differentiated cells. There was also a significant reduction in mitochondrial membrane potential (Deltapsi m) and a leakage of cytochrome c from mitochondria into the cytosol of myocytes differentiated from Smad5 mutant ES cells. The expression of p53 and p21 was found to be elevated in the differentiated Smad5 mutant myocytes, and this was accompanied by an up-regulation in caspase 3 expression. These results suggest that the Smad5-mediated TGF-beta signals may protect cardiomyocytes from apoptosis by maintaining the integrity of the mitochondria, probably through suppression of p53 mediated pathways.

Animals↗

PubMed2005

Solution structure of human SUMO-3 C47S and its binding surface for Ubc9.

Small ubiquitin-related modifier SUMO-3 is a member of a growing family of ubiquitin-like proteins (Ubls). So far, four isoforms of SUMO have been identified in humans. It is generally known that SUMO modification regulates protein localization and activity. Previous structure and function studies have been mainly focused on SUMO-1. The sequence of SUMO-3 is 46% identical with that of SUMO-1; nevertheless, functional heterogeneity has been found between the two homologues. Here we report the solution structure of SUMO-3 C47S (residues 14-92) featuring the beta-beta-alpha-beta-beta-alpha-beta ubiquitin fold. Structural comparison shows that SUMO-3 C47S resembles ubiquitin more than SUMO-1. On the helix-sheet interface, a strong hydrophobic interaction contributes to formation of the globular and compact fold. A Gly-Gly motif at the C-terminal tail, extending away from the core structure, is accessible to enzymes and substrates. In vivo, SUMO modification proceeds via a multistep pathway, and Ubc9 plays an indispensable role as the SUMO conjugating enzyme (E2) in this process. To develop a better understanding of SUMO-3 conjugation, the Ubc9 binding surface on SUMO-3 C47S has been detected by chemical shift perturbation using NMR spectroscopy. The binding site mainly resides on the hydrophilic side of the beta-sheet. Negatively charged and hydrophobic residues of this region are highly or moderately conserved among SUMO family members. Notably, the negatively charged surface of SUMO-3 C47S is highly complementary in its electrostatic potentials and hydrophobicity to the positively charged surface of Ubc9. This work indicates dissimilarities between SUMO-3 and SUMO-1 in tertiary structure and provides insight into the specific interactions of SUMO-3 with its modifying enzyme.

Amino Acid Sequence↗