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Biomedical subjects

Yi Wang

Publications and source records attributed to Yi Wang.

At least 73 records · Page 4Linked to original sources

Polymorphisms in DNA damage binding protein 2 (DDB2) and susceptibility of primary lung cancer in the Chinese: a case-control study.

DNA damage binding protein 2 (DDB2) is one of the major DNA repair proteins involved in the nucleotide excision repair (NER) pathway. Mutations in the DDB2 gene can cause a repair-deficiency syndrome xeroderma pigmentosum group E. Because tobacco carcinogens can cause DNA damage that is repaired by NER and suboptimal NER capacity is reported to be associated with lung cancer risk, we hypothesized that common variants in the DDB2 gene are associated with lung cancer risk. To test this hypothesis, we conducted a case-control study of 1010 patients with incident lung cancer and 1011 cancer-free controls and genotyped two DDB2 single nucleotide polymorphisms (SNPs) (rs830083 and rs3781620) that are in linkage disequilibrium with other untyped SNPs. We found that compared with the rs830083CC, subjects carrying the heterozygous rs830083CG genotype had a significantly 1.31-fold increased risk of lung cancer [95% confidence interval (CI) 1.08-1.60] and those carrying the homozygous rs830083GG genotype had a non-significantly 1.22-fold elevated risk (95% CI 0.89-1.67). In addition, effects of the combined rs830083CG/GG variant genotypes were more evident in young subjects, heavy smokers and subjects with a positive family history of cancer. These findings indicate, for the first time, that the DDB2 rs830083 polymorphism may contribute to the etiology of lung cancer. Further functional studies on this SNP and/or related variants are warranted to elucidate the underlying molecular mechanisms of the association.

Aged↗

Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics.

BACKGROUND & AIMS: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, target liver HMG-CoA and are of proven benefit in the prevention of coronary heart disease. Rosuvastatin is an effective statin notable for liver selectivity and lack of significant metabolism. We assessed the extent and relevance of hepatic transporters to rosuvastatin uptake. METHODS: Transporters involved in rosuvastatin uptake were determined through heterologous expression of multiple human and rat uptake transporters. Human organic anion transporting polypeptide (OATP) 1B1 and sodium-dependent taurocholate cotransporting polypeptide (NTCP) allelic variants were also assessed. Expression of OATP and NTCP messenger RNA and protein was determined from a bank of human liver samples. RESULTS: Multiple OATP family members, including 1B1, 1B3, 2B1, and 1A2, were capable of rosuvastatin transport. Naturally occurring polymorphisms in OATP1B1, including *5, *9, *15, and *18, were associated with profound loss of activity toward rosuvastatin. Interestingly, the major human hepatic bile acid uptake transporter NTCP, but not rat Ntcp, also transported rosuvastatin. Human hepatocyte studies suggested that NTCP alone accounted for approximately 35% of rosuvastatin uptake. Remarkably, NTCP*2, a variant known to have a near complete loss of function for bile acids, exhibited a profound gain of function for rosuvastatin. Quantitative messenger RNA analysis revealed marked intersubject variability in expression of OATPs and NTCP. CONCLUSIONS: Multiple transporters mediate the overall hepatic uptake of rosuvastatin, and NTCP may be a heretofore unrecognized transporter important to the disposition of rosuvastatin and possibly other drugs/statins in clinical use. Accordingly, transporter expression and polymorphisms may be key determinants of intersubject variability in response to statin therapy in general.

Animals↗

The in-vitro bioactivity of mesoporous bioactive glasses.

Ordered mesoporous bioactive glasses (MBGs) with different compositions were prepared by using nonionic block copolymer surfactants as structure-directing agents through an evaporation-induced self-assembly process. Their in-vitro bioactivities were studied in detail by electron microscopy, Fourier-transform infrared spectroscopy, and inductively coupled plasma (ICP) atomic emission spectroscopy. The ICP element analysis results were further calculated in terms of the total consumption of Ca and P, Delta[Ca]/Delta[P] ratios, and ionic activity product (IP) of hydroxyapatite. Through the above analysis, it is clear that MBGs show a different structure-bioactivity correlation compared to conventional sol-gel-derived BGs. The in vitro bioactivity of MBGs is dependent on the Si/Ca ratio in the network when the other material parameters such as the mesostructure and texture properties (pore size, pore volume) are controlled. MBG 80S15C with relatively lower calcium content exhibits the best in vitro bioactivity, in contrast to conventional sol-gel-derived BGs where usually higher calcium percentage BGs (e.g. 60S35C) show better bioactivity. Calcination temperature is another important factor that influences the in vitro bioactivity. According to our results, MBGs calcined at 973K may possess the best in vitro bioactivity. The influences of the composition and calcination temperature upon bioactivity are explained in terms of the unique structures of MBGs.

Bone Substitutes↗

Effects of sodium arsenite on catalase activity, gene and protein expression in HaCaT cells.

The objective of this research work is to study the effects of sodium arsenite on activity, mRNA and protein expression of catalase (CAT) in established human cell lines of keratinocytes (HaCaT). Based on the AlamarBlue assay, we found that a high level (100 micromol/l) of sodium arsenite inhibited cell viability. The reactive oxygen species (ROS) content in cells was increased in all treated cultures dose-dependently. CAT activity, mRNA expression and protein levels were decreased by 5-20 micromol/l of sodium arsenite. It is highly suggestive that CAT gene expression and protein levels are affected by arsenic.

Arsenites↗

[Malaria situation in the People' s Republic of China in 2004].

In 2004, 38,972 malaria cases and 106,704 suspected cases with 31 deaths were reported by the annual case reporting system in 1,005 counties of 23 Provinces/Municipality/Autonomous Region (P/ M/A) and the annual incidence was 0.38/10 000, a decrease of 4.2% than that of the last year, which is the year that the disease was slightly rolled back after consecutively increased since 2001. As an important development of the case reporting system, the internet reporting system started in 2004, majority of the malaria cases (38 254) were reported through internet from 1,074 counties of all the 30 P/M/A except Qinghai Province. Among the 1,005 counties with reported malaria cases, 32 counties were with an incidence of more than 10/10,000 distributing in Yunnan (19 counties), Hainan (10) and Anhui (3). There were 61 counties in which the malaria incidence was between 1/10,000 and 10/10,000. The number of Plasmodium falciparum malaria cases was 4,891, accounting for 12.6% of the total cases, of which 35.0% (1,714) were imported cases reported in 174 counties/cities of 18 P/M/A. Indigenous falciparum malaria was found in 45 counties/ cities of Yunnan and Hainan Provinces, of which 29 counties/cities were in Yunnan, decreased by 35, 16 were in Hainan, increased by 2 compared to that of 2003. Yunnan and Hainan Provinces are still the relatively high transmission areas. Yunnan has ranked No. 1 in the country in terms of the number of cases while Hainan ranked No. 1 by malaria incidence in recent years. 22 247 malaria cases were reported from the two provinces in 2004, accounting for 57.1% of the total reported cases in the country. There were 12,865 cases with 25 deaths reported from Yunnan, and the incidence was 3.09/10,000, a decrease of 16.6% than that in the last year. Among the reported cases, 3,251 were falciparum malaria, decreased by 7.9% in comparison to 2003. The number of reported cases in Hainan was 9 832, with an incidence of 11.64/10 000, 46.6% increase than the last year. In central China, the re-emergence of malaria was considerable in provinces along the Huai River, especially in Anhui Province. The case number in Anhui has been the second or third largest in the country since 2001. 8909 malaria cases and 14,542 suspected cases were reported from the Province in 2004, accounting for 22.9% of the total cases in the country, with an incidence of 1. 38/10,000 increased by 9.8% than that in 2003. Hubei reported 2,714 malaria cases with an incidence of 0.47/10,000, decreased by 60.8%. The number of reported cases in Henan was 2,211, decreased by 43.1%. 676 cases were reported from Jiangsu, almost the same as that in 2003. Focal outbreaks occurred in 109 villages of 13 counties in Anhui, Hubei and Jiangsu, where Anopheles sinensis is the principal transmission vector. Malaria cases reported from the above 4 provinces accounted for 37.2% of the national figure. Cases reported from Guizhou, Sichuan, Guangxi, Guangdong, Zhejiang, Shanghai and Hunan in southeast China occupied about 5% of the total cases, over 50% of which were imported cases. Less than 100 cases were reported from each of Fujian, Chongqing, Shandong, Jiangxi, Liaoning, Shaanxi, Shanxi, Gansu, Xinjiang and Heilongjiang Provinces in the year. In summary, although malaria cases slightly decreased after several years' consecutive increase, malaria is still an important problem of public health in China, especially in the southern and central parts. Yunnan and Hainan still face a critical situation of malaria endemics with the spread of P.falciparum, especially in the 25 border counties in Yunnan. In central parts of the country, especially in Anhui, malaria prevalence was highly unstable with frequent focal outbreaks in areas along the Huai River, which reveals new challenges to the national malaria control program.

China↗

The role of pH in the fermentative H2 production from an acidogenic granule-based reactor.

The role of pH in the fermentative H(2) production from an upflow acidogenic granule-based reactor was investigated in this study. Experimental results show that all H(2) partial pressure, H(2) production rate and H(2) yield were pH-dependent, in the range of 2.8 x 10(4)-5.2 x 10(4)Pa, 61-145 ml-H(2)l(-1)h(-1) and 0.68-1.61 mol-H(2)mol-glucose(-1), respectively. The maximum H(2) partial pressure was observed at pH 3.4, while both maximum H(2) production rate and H(2) yield were found at pH 4.2. Acetate, propionate, butyrate, i-butyrate, valerate, caporate and ethanol were present in the effluent of this UASB reactor, and their distribution was also pH-dependent. As pH was decreased from 4.2 to a lower level of 3.4 or increased to a higher level of 6.3, the fermentative type of this H(2)-producing reactor would shift from butyrate-type to caporate- or ethanol-type. Thermodynamic analysis was performed to explore the possible metabolic pathways of caproate and valerate formation. The metabolic pathway of caproate formation was pH-dependent, while that of valerate formation was pH-independent. A neural network model was designed, trained and validated. It was able to successfully describe the daily variations of H(2) partial pressure and H(2) yield of the reactor, and to predict its steady state performance at various pHs.

Anaerobiosis↗

V2 thin stripes contain spatially organized representations of achromatic luminance change.

A considerable amount of research over the last decades has focused on the apparent specialization of V2 thin stripes for the processing of color in diurnal primates. However, because V2 thin stripes are functionally heterogeneous in that they consist of largely separate color- and luminance-preferring domains and because the color-preferring domains contain a systematic representation of hue, we hypothesized that they contained functional maps that subserve luminance processing. Here we show, using optical imaging of intrinsic cortical signals and microelectrode recording, that the V2 thin stripe luminance-preferring domains contain spatially segregated modules that encode the direction of relative luminance change. Quantitative analysis of the cortical responses to luminance increments or decrements indicates that these luminance-sensitive modules also encode the magnitude of the luminance change by the magnitude of the evoked cortical response. These results demonstrate an important role of V2 thin stripes in the processing of luminance and thus suggest that thin stripes are involved in the overall processing of the surface properties of objects rather than simply the processing of color.

Animals↗

Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice.

Pleomorphic adenoma gene 1 (PLAG1) was found frequently rearranged and activated in human salivary gland pleomorphic adenomas. It encodes a developmentally regulated transcription factor. Ectopic overexpression of PLAG1 has been proposed to play a crucial role in tumorigenesis of salivary gland pleomorphic adenomas. It was reported that PLAG1 can activate the transcription of insulin-like growth factor 2 (IGF2), functioning as a protooncogene. In this report, we show that the salivary gland tumors developed in PLAG1 transgenic mice share major histopathologic features with human pleomorphic adenomas. It was found that beta-catenin, the key component of Wnt signaling pathway, was upregulated at transcriptional level in tumors developed in 3 independent transgenic mouse lines. Immunohistochemical staining revealed that expression of beta-catenin as well as c-myc, downstream of beta-catenin in Wnt signaling pathway, was highly upregulated with overexpression of PLAG1 transgene in tumor and normal transgenic salivary gland tissues. Moreover, we found that PLAG1 can activate the transcription of mouse but not human beta-catenin in the 3T3 cells cotransfected with reporter constructs. Sequence analysis shows there are 4 PLAG1 consensus binding sites in mouse beta-catenin promoter region but not in human. Our findings provide the first in vivo evidence for the oncogenic activity of PLAG1 in pleomorphic adenoma tumorigenesis, reveal a valued animal model for human salivary gland tumors and suggest that Wnt signaling pathway may also contribute to the development of pleomorphic adenomas in transgenic mice.

3T3 Cells↗

Linkage disequilibrium sharing and haplotype-tagged SNP portability between populations.

The discovery of the block-like structure of linkage disequilibrium (LD) in human populations holds the promise of delineating the etiology of common diseases. However, understanding the magnitude, mechanism, and utility of between-population LD sharing is critical for future genome-wide association studies. In this study, substantial LD sharing between six non-African populations was observed, although much less between African-American and non-African, based on 20,000 SNPs of chromosome 21. We also demonstrated the respective roles of recombination and demographic events in shaping LD sharing. Furthermore, we showed that the haplotype-tagged SNPs chosen from one population are portable to the others in East Asia. Therefore, we concluded that the magnitude of LD sharing between human populations justifies the use of representative populations for selecting haplotype-tagged SNPs in genome-wide association studies of complex diseases.

Africa↗

ATP-dependent transport of rosuvastatin in membrane vesicles expressing breast cancer resistance protein.

MDR1/ABCB1, MRP2/ABCC2, and breast cancer resistance protein (BCRP)/ABCG2 are expressed in the liver and intestine and contribute to the disposition of many drugs. Rosuvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor for the treatment of patients with dyslipidemia, is primarily excreted via bile as unchanged drug. The present study was designed to determine whether rosuvastatin is transported by MDR1, MRP2, and BCRP. The apparent permeability value for rosuvastatin across MDR1-Madin-Darby canine kidney cells was low ( approximately 8 nm/s), and no directional transport was observed. Rosuvastatin uptake into control Sf9 membranes and membranes expressing MRP2 was similar in the presence or absence of GSH. In contrast, ATP dramatically stimulated rosuvastatin uptake into membranes expressing BCRP, but not control membranes. Rosuvastatin transport occurred into an osmotically sensitive space and was saturable. An Eadie-Hofstee analysis suggested that there were two transport sites in BCRP, with an apparent K(m) of 10.8 muM for the high affinity site and 307 microM for the low affinity site. These data demonstrate that rosuvastatin is transported efficiently by BCRP and suggest that BCRP plays a significant role in the disposition of rosuvastatin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Breath-hold 3D steady-state free precession coronary MRA compared with conventional X-ray coronary angiography.

PURPOSE: To evaluate the use of breath-hold three-dimensional (3D) steady-state free precession (SSFP) coronary magnetic resonance angiography (MRA) in patients with coronary artery disease (CAD) in comparison with conventional coronary x-ray angiography (XRA). MATERIALS AND METHODS: Twenty-eight patients with suspected CAD were examined with the use of a breath-hold 3D-SSFP-MRA sequence and conventional XRA. To assess the accuracy of MRA, two clinicians who were blinded to patient information independently reviewed the MRA and XRA data, which were presented in a randomized order. To identify discrepancies between MRA and XRA, and assess features of coronary lesions on MRA, two additional clinicians examined MRA and XRA data that were presented side by side, divided into proximal, mid, and distal segments, and compared them segment by segment. RESULTS: The sensitivity and specificity for diagnosing significant coronary stenoses (> 50% diameter narrowing) were 64% and 94%, respectively. At sites of coronary lesions identified on XRA, bright signals and enlarged vessel profiles, in addition to the characteristic narrow lumen, were frequently observed on MRA. CONCLUSION: Breath-hold SSFP coronary MRA has good specificity but inconclusive sensitivity in diagnosing significant coronary stenoses, and provides important image features for depicting coronary lesions.

Adult↗

Delayed hyperenhancement patterns in occlusive and reperfused myocardial infarcts during different healing stages.

PURPOSE: To investigate delayed hyperenhancement during different healing stages of myocardial infarct with and without reperfusion in a pig model. MATERIALS AND METHODS: Twelve pigs were studied. Six pigs were subjected to permanent right coronary artery (RCA) occlusion, and the other six were subjected to transient 90-minute RCA occlusion. In vivo MRI including first-pass perfusion and myocardial delayed enhancement (MDE) was performed at four, eight, 12, and 24 hours, and eight days after the artery occlusion. The MDE scan was repeated four times, two to 32 minutes after contrast administration. RESULTS: For all six pigs without reperfusion, the four-hour MRI showed transmural perfusion defect and no delayed hyperenhancement; from eight hours on, delayed hyperenhancement appeared and its spatial extent gradually increased until it became transmural hyperenhancement at eight days. However, in all six pigs with reperfusion, hyperenhancement was present at every stage from four hours to eight days. Pathology confirmed the existence of infarct at various stages of healing irrespective of reperfusion status. CONCLUSION: Occlusive hyperacute infarct did not exhibit any delayed hyperenhancement, which indicates that perfusion plays an important role in delayed enhancement at the hyperacute stage.

Animals↗

Automatic algorithm for correcting motion artifacts in time-resolved two-dimensional magnetic resonance angiography using convex projections.

Time-resolved contrast enhanced magnetic resonance angiography (MRA) may suffer from involuntary patient motion. It is noted that while MR signal change associated with motion is large in magnitude and has smooth phase variation in k-phase, signal change associated with vascular enhancement is small in magnitude and has rapid phase variation in k-space. Based upon this observation, a novel projection onto convex sets (POCS) algorithm is developed as an automatic iterative method to remove motion artifacts. The presented POCS algorithm consists of high-pass phase filtering and convex projections in both k-space and image space. Without input of detailed motion knowledge, motion effects are filtered out, while vasculature information is preserved. The proposed method can be effective for a large class of nonrigid motions, including through-plane motion. The algorithm is stable and converges quickly, usually within five iterations. A double-blind evaluation on a set of clinical MRA cases shows that a completely unsupervised version of the algorithm produces significantly better rank scores (P=0.038) when compared to angiograms produced manually by an experienced radiologist.

Algorithms↗

Cardiac fat navigator-gated steady-state free precession 3D magnetic resonance angiography of coronary arteries.

Motion artifacts and the lack of accurate detection of cardiac motion present a major challenge for high-resolution cardiac MRI. Recently a multidimensional cardiac fat navigator was proposed to provide a fast and direct measurement of bulk cardiac motion. The objective of this study was to demonstrate the feasibility of employing the cardiac fat navigator in balanced steady-state free precession (SSFP) free-breathing 3D coronary MRA (CMRA). The cardiac fat navigator echo is optimized to provide both motion monitoring and epicardial fat suppression. Steady-state magnetization preparation, which is needed for SSFP CMRA, is optimized by comparing three preparation schemes: alpha/2, linear ramp with 20 RF pulses (20LR), and Kaiser ramp with six RF pulses (6KR). The present preliminary human study shows that the 6KR preparation provides better image quality than both the alpha/2 (P<0.0025) and the 20LR preparations (P<0.025) for free-breathing SSFP 3D CMRA (N=11).

Adipose Tissue↗

Decomposed direct matrix inversion for fast non-cartesian SENSE reconstructions.

A new k-space direct matrix inversion (DMI) method is proposed here to accelerate non-Cartesian SENSE reconstructions. In this method a global k-space matrix equation is established on basic MRI principles, and the inverse of the global encoding matrix is found from a set of local matrix equations by taking advantage of the small extension of k-space coil maps. The DMI algorithm's efficiency is achieved by reloading the precalculated global inverse when the coil maps and trajectories remain unchanged, such as in dynamic studies. Phantom and human subject experiments were performed on a 1.5T scanner with a standard four-channel phased-array cardiac coil. Interleaved spiral trajectories were used to collect fully sampled and undersampled 3D raw data. The equivalence of the global k-space matrix equation to its image-space version, was verified via conjugate gradient (CG) iterative algorithms on a 2x undersampled phantom and numerical-model data sets. When applied to the 2x undersampled phantom and human-subject raw data, the decomposed DMI method produced images with small errors (< or = 3.9%) relative to the reference images obtained from the fully-sampled data, at a rate of 2 s per slice (excluding 4 min for precalculating the global inverse at an image size of 256 x 256). The DMI method may be useful for noise evaluations in parallel coil designs, dynamic MRI, and 3D sodium MRI with fixed coils and trajectories.

Algorithms↗

Reduction of reconstruction time for time-resolved spiral 3D contrast-enhanced magnetic resonance angiography using parallel computing.

Time-resolved 3D MRI with high spatial and temporal resolution can be achieved using spiral sampling and sliding-window reconstruction. Image reconstruction is computationally intensive because of the need for data regridding, a large number of temporal phases, and multiple RF receiver coils. Inhomogeneity blurring correction for spiral sampling further increases the computational work load by an order of magnitude, hindering the clinical utility of spiral trajectories. In this work the reconstruction time is reduced by a factor of >40 compared to reconstruction using a single processor. This is achieved by using a cluster of 32 commercial off-the-shelf computers, commodity networking hardware, and readily available software. The reconstruction system is demonstrated for time-resolved spiral contrast-enhanced (CE) peripheral MR angiography (MRA), and a reduction of reconstruction time from 80 min to 1.8 min is achieved.

Algorithms↗

Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and its effect on lectin-like oxidized low density lipoprotein receptor-1 expression in rabbits.

OBJECTIVE: To investigate the prevention by Tongxinluo capsule (TXL) of vascular lesions and its effect on the levels of protein and gene expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in rabbits with atherosclerosis (AS), and to explore its possible mechanism against AS. METHODS: AS models were established by feeding New Zealand white rabbits with high-cholesterol diet, and 24 immature rabbits were randomly divided into the control group, model group and treated group (treated with TXL capsule). The indexes of total cholesterol (TC) and low density lipoprotein (LDL) levels were measured at the 16th week. The intima thickness and the plaque area of abdominal aorta were quantitatively analyzed by pathological morphological analysis, the expression of macrophage and smooth muscle cell (SMC) in intima were detected by immunohistochemical method and histologic segments were stained by Hematoxilin-Eosin (HE) to identify the degree of atherosclerotic lesion in the model group and the prevention by TXL. The LOX-1 gene and protein expression in abdominal aorta was detected by semi-quantitative RT-PCR and immunohistochemistry, respectively. RESULTS: In the model group, the levels of TC and LDL were significantly elevated, aortic intima thickened extensively, the intima area enhanced, and macrophages expression increased; the levels of LOX-1 gene and protein expression was up-regulated in endothelium and neo-intima of the abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial intimal proliferation, markedly inhibited the expression of macrophage and excessively expressed the level of LOX-1. CONCLUSION: TXL has an inhibitory effect on blood lipids, and it can prevent the occurrence of vascular lesion and cure its development, and its protection against AS was possibly associated with a crucial endothelial protective action through lowering the expression of LOX-1 in vascular walls.

Actins↗