Biomedical subjects

Xin Xu

Publications and source records attributed to Xin Xu.

At least 73 records · Page 4Linked to original sources

PubMed2005

[Strategies for handling the insufficiency of the proximal landing zone during endovascular thoracic aortic repair].

OBJECTIVE: To discuss two strategies for handling the insufficiency of the proximal landing zone (PLZ) during endovascular thoracic aortic repair. METHODS: Ten patients underwent endovascular repair (EVR) in the thoracic aorta in one year. Nine patients had DeBakey type III aortic dissection aneurysm (ADA), and one had descending thoracic aortic aneurysm (DTAA). The PLZ, defined as the distance from the origin of the left subclavian artery (LSA) to the primary entry tear of the dissection or the proximal aspect of DTAA, was measured less than 15 mm in all instances by contrast-enhanced CT scan and digital subtraction angiography. The preliminary carotid-carotid and left carotid-subclavian bypass combined with EVR was employed in the DTAA and 3 ADA cases, and the EVR with the intentional coverage of the LSA without the preliminary bypass in the rest 6 ADA patients. RESULTS: The technical success was achieved in all instances. The case of DTAA died of the hemispheric cerebral infarction and subsequent multiple system organ failure, albeit the uneventful recovery from the prior cervical reconstruction. Dizziness occurred in 2 patients (ADA) after the EVR with the intentional bypass-absent coverage of the LSA, but noticeably resolved after the intravenous administration of mannitol for 4 to 5 days. No neurological deficits or limb ischemia developed perioperatively or during the follow-up range from 3 to 12 months. And complete thrombosis of the thoracic aortic false lumen and enlargement of the true lumen were revealed on CT at 3 months in all 9 patients with ADA. CONCLUSIONS: Both the adjunctive surgical bypass and the intentional bypass-absent coverage of the left subclavian artery appear feasible in handling the insufficiency of the proximal landing zone during the endovascular thoracic aortic repair. It can expand the EVR applicability in management of DeBakey type III ADAs and DTAAs.

Adult↗

PubMed2005

A time dependent density functional theory study of alpha-84 phycocyanobilin chromophore in C-phycocyanin.

The optical characteristics of absorption and circular dichroism (CD) spectroscopy of an alpha-subunit of C-phycocyanin (C-PC) were investigated by using time dependent density functional theory (TDDFT) combined with the polarizable continuum model (PCM). When the protonation of alpha-84 phycocyanobilin (PCB) and its interaction with the protein moiety in C-PC have been taken into account, satisfactory assignment of the absorption and CD spectra of alpha-84 PCB can be achieved. The TDDFT-PCM calculations conclude that in the visible absorption region the main peak arises from the pi electron excitation of the pyrrole rings and the shoulder peak comes from the charge transfer from Asp87 (a nearby amino acid residue) to PCBH(+).

Circular Dichroism↗

PubMed2005

Synthesis and biological evaluation of sulfonamidooxazoles and beta-keto sulfones: selective inhibitors of 11beta-hydroxysteroid dehydrogenase type I.

The design, synthesis, and biological evaluation of arylsulfonamidooxazoles as 11beta-HSD1 inhibitors and the serendipitous discovery of beta-keto sulfones as potent 11beta-HSD1 inhibitors are described here. These two classes of compounds are not active against 11beta-HSD2 and therefore may have significant therapeutic potential for metabolic syndrome, type 2 diabetes and related metabolic dysfunctions.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗

PubMed2005

Growth of silver nanowires from solutions: a cyclic penta-twinned-crystal growth mechanism.

Silver nanowires are synthesized by simple reduction of the silver ions with reductants such as glucose, sodium citrate, and sodium hypophosphite, etc., in the absence of the so-called surfactants or capping reagents at the temperature from 80 to 200 degrees C. Regardless of the reductants, the nanowires prepared at a given temperature are uniform in diameters, ranging from 30 to 50 nm at 100 degrees C. Nanoparticles coexist with nanowires in the products with larger diameters (usually larger than 50 nm). We find that all the silver nanowires in the as-prepared products are of cyclic penta-twinned structure, where five crystallites bond by the {111} facets. We propose that the intrinsic factor of the cyclic penta-twinned structure, i.e., the angular mismatch of the five crystallites in forming a gapless rod, controls the size of the nanowires and guides the directional growth of the nanowires with {110} as the active facets. The nanoparticles in the products are aggregates of imperfect penta-twinned crystals, which inhibits them from growing into nanowires and results in larger size. From the structural information of the nanoparticles synthesized at room temperature, we propose that the formation of the cyclic penta-twinned structure is due to the stacking fault and the intrinsic equilibrium structures of the lower energy.

Journal Article↗

PubMed2005

Changes of ECM and CAM gene expression profile in the cirrhotic liver after HCV infection: analysis by cDNA expression array.

AIM: We aimed to observe the expression of extracellular matrix (ECM) and cellular adhesion molecules (CAM) in cirrhotic liver tissues after hepatitis C virus (HCV) infection. METHODS: Twelve patients with post HCV inflammatory liver cirrhosis were selected to evaluate their liver function and other virological, pathological parameters. Then three specimens of cirrhotic patients whose health assessment results and laboratory data were similar and three normal liver specimens explanted from liver grafts prepared for liver transplantation were chosen for investigating gene expression of ECM and CAM using cDNA expression array. RESULTS: The cDNA array assay revealed 36.7% (36/96) of genes with changes, in which 26.3% (26/96) was up-regulated and 10.1% (10/96) was down-regulated. Integrin (ITGA), collagen (COL), ADAMTS were identified as the characteristic changes of ECM and CAM gene expression levels. ITGA were demonstrated beta1 and beta2 sub-section changed in liver cirrhosis. CONCLUSION: ECM and CAM play an important role in the progression of liver cirrhosis after HCV infection. The capital mechanism is related to the inflammatory cells infiltration, the activation and transformation of ECM producing cells and the imbalance between production and elimination of ECM.

Adult↗

PubMed2005

Mechanisms of initial propane activation on molybdenum oxides: a density functional theory study.

We report the first detailed density functional theory study on the mechanisms of initial propane activation on molybdenum oxides. We consider 6 possible mechanisms of the C-H bond activation on metal oxides, leading to 17 transition states. We predict that hydrogen abstraction by terminal Mo=O is the most feasible reaction pathway. The calculated activation enthalpy and entropy are 32.3 kcal/mol and -28.6 cal/(mol/K), respectively, in reasonably good agreement with the corresponding experimental values (28.0 kcal/mol and -29.1 cal/(mol/K)). We find that activating the methylene C-H bond is 4.7 kcal/mol more favorable than activating the methyl C-H bond. This regioselectivity is correlated with the difference in strength between a methylene C-H bond and a methyl C-H bond. Our calculations suggest that a combined effect from both the methylene and the methyl C-H bond cleavages leads to the experimentally observed overall kinetic isotopic effects from propane to propylene on the MoO(x)/ZrO(2) catalysts.

Journal Article↗

PubMed2005

Mechanisms of methane activation and transformation on molybdenum oxide based catalysts.

We present a comprehensive survey of different C-H activation pathways over various kinds of active sites of terminal oxygens [=O] and bridge oxygens [-O-] by using Mo3O9 model systems. This allows us to provide some insights into fundamental issues concerning C-H activation by metal oxo species involved in many heterogeneous, homogeneous, and enzymatic processes. We show that H abstraction is the most feasible reaction pathway for the activation of a C-H bond on molybdenum oxides; and that [=O] is more active than [-O-]. Our calculations also suggest that (2+2) can be an alternative if M=O bond possesses a high polarity, while (5+2) can provide another effective pathway if two M=O bonds are in close proximity. Implications for the related heterogeneous, homogeneous, and enzymatic processes are discussed.

Journal Article↗

PubMed2005

Application of atomic force microscopy in blood research.

AIM: To find suitable solutions having lesser granules and keeping erythrocytes in normal shapes under atomic force microscopy (AFM). METHODS: Eight kinds of solutions, 1% formaldehyde, PBS buffer (pH7.2), citrate buffer (pH 6.0), 0.9% NaCl, 5% dextrose, TAE, 1640 medium and 5% EDTA-K2, were selected from commonly used laboratory solutions, and venous blood from a healthy human volunteer was drawn and anticoagulated with EDTA-K2. Before scanned by AFM (NanoScopeIIIa SPM, Digital Instruments, Santa Barbara, CA), a kind of intermixture was deposited on freshly cleaved mica and then dried in the constant temperature cabinet (37 degrees). RESULTS: One percent formaldehyde, citrate buffer, 5% dextrose, TAE, were found to keep human erythrocytes in normal shape with few particles. Processed by these solutions, fine structures of human erythrocyte membrane were obtained. CONCLUSION: One percent formaldehyde, citrate buffer, 5% dextrose and TAE may be applied to dispose erythrocytes in AFM. The results may offer meaningful data for clinical diagnosis of blood by AFM.

Buffers↗

PubMed2005

SNPHunter: a bioinformatic software for single nucleotide polymorphism data acquisition and management.

BACKGROUND: Single nucleotide polymorphisms (SNPs) provide an important tool in pinpointing susceptibility genes for complex diseases and in unveiling human molecular evolution. Selection and retrieval of an optimal SNP set from publicly available databases have emerged as the foremost bottlenecks in designing large-scale linkage disequilibrium studies, particularly in case-control settings. RESULTS: We describe the architectural structure and implementations of a novel software program, SNPHunter, which allows for both ad hoc-mode and batch-mode SNP search, automatic SNP filtering, and retrieval of SNP data, including physical position, function class, flanking sequences at user-defined lengths, and heterozygosity from NCBI dbSNP. The SNP data extracted from dbSNP via SNPHunter can be exported and saved in plain text format for further down-stream analyses. As an illustration, we applied SNPHunter for selecting SNPs for 10 major candidate genes for type 2 diabetes, including CAPN10, FABP4, IL6, NOS3, PPARG, TNF, UCP2, CRP, ESR1, and AR. CONCLUSION: SNPHunter constitutes an efficient and user-friendly tool for SNP screening, selection, and acquisition. The executable and user's manual are available at http://www.hsph.harvard.edu/ppg/software.htm

Algorithms↗

PubMed2005

A novel thiazolidinedione MCC-555 down-regulates tumor necrosis factor-alpha-induced expression of vascular cell adhesion molecule-1 in vascular endothelial cells.

Thiazolidinediones (TZDs) are anti-diabetic agents that enhance insulin sensitivity through activating peroxisome proliferator-activated receptor (PPAR) gamma. Besides their glucose-lowering effects, TZDs are shown to exhibit anti-inflammatory properties in vascular cells, although their precise molecular mechanisms are unknown. In the present study, we examined the effects of a novel TZD MCC-555, which has unique characteristics of ability to activate not only PPARgamma but also PPARalpha and PPARdelta on vascular cell adhesion molecule-1 (VCAM-1) expression in vascular endothelial cells (ECs). Human aortic ECs were treated with MCC-555, followed by stimulation with tumor necrosis factor (TNF)-alpha. Cell surface VCAM-1 protein expression and human monocytoid U937 cell adhesion to these cells were determined. MCC-555 efficiently inhibited TNF-alpha-stimulated VCAM-11expression and U937 cell adhesion. Transient transfection of bovine aortic ECs with a VCAM-1 promoter construct revealed that MCC-555 inhibited TNF-alpha-induced VCAM-1 promoter activity. Electrophoretic mobility-shift assay demonstrated that MCC-555 reduced the amount of nuclear factor-kappaB (NF-kappaB) bound to its recognition site on the VCAM-1 promoter. The considered PPARdelta activator GW501516 and the considered PPARalpha activator fenofibrate also inhibited TNF-alpha-induced VCAM-1 expression, whereas pioglitazone and rosiglitazone did not. These results indicate that MCC-555 is a strong TZD agent to inhibit the cytokine-induced VCAM-1 expression in vascular ECs. This effect is exerted probably through activation of PPARalpha and/or PPARdelta, rather than PPARgamma, mediating down-regulation of NF-kappaB activity.

Aorta↗

PubMed2005

Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells.

Previous studies have indicated an intimate linkage between gap junction and adherens junction formation. It was suggested this could reflect the close membrane-membrane apposition required for junction formation. In NIH3T3 cells, we observed the colocalization of connexin43 (Cx43alpha1) gap junction protein with N-cadherin, p120, and other N-cadherin-associated proteins at regions of cell-cell contact. We also found that Cx43alpha1, N-cadherin, and N-cadherin-associated proteins were coimmunoprecipitated by antibodies to either Cx43alpha1, N-cadherin, or various N-cadherin-associated proteins. These findings suggest that Cx43alpha1 and N-cadherin are coassembled in a multiprotein complex containing various N-cadherin-associated proteins. Studies using siRNA knockdown indicated that cell surface expression of Cx43alpha1 required N-cadherin, and conversely, N-cadherin cell surface expression required Cx43alpha1. Pulse-chase labeling and cell surface biotinylation experiments indicated that in the absence of N-cadherin, Cx43alpha1 cell surface trafficking is blocked. Surprisingly, siRNA knockdown of p120, an N-cadherin-associated protein known to modulate cell surface turnover of N-cadherin, reduced N-cadherin cell surface expression without altering Cx43alpha1 expression. These observations suggest that in contrast to the coregulated cell surface trafficking of Cx43alpha1 and N-cadherin, N-cadherin turnover at the cell surface may be regulated independently of Cx43alpha1. Functional studies showed gap junctional communication is reduced and cell motility inhibited with N-cadherin or Cx43alpha1 knockdown, consistent with the observed loss of both gap junction and cadherin contacts with either knockdown. Overall, these studies indicate that the intracellular coassembly of connexin and cadherin is required for gap junction and adherens junction formation, a process that likely underlies the intimate association between gap junction and adherens junction formation.

Adherens Junctions↗

PubMed2005

Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.

Airway hyperresponsiveness (AHR) is one of the major clinical symptoms and intermediate phenotypes of asthma. A recent genome-wide search for asthma quantitative trait loci has revealed a significant linkage signal between a p-terminal region of chromosome 2 and AHR. Thus, the gene encoding the potassium voltage-gated channel delayed-rectifier protein S3 (KCNS3) in this region is considered a positional candidate for asthma. We have evaluated a total of 12 single-nucleotide polymorphisms (SNPs) of the KCNS3 gene in a validation panel of 48 lymphoblastoid cell line DNA samples of Chinese origin. Three SNPs were found to be polymorphic and were tested. Two independent sets (an initial screening set and a replication set) of cases and controls from the original linkage study sample were collected. In the initial screening set, two SNPs (rs1031771 and rs1031772) showed suggestive association and were further confirmed by the replication set. In combined single-SNP analysis, the rs1031771 G allele (odds ratio=1.42, P=0.006) and rs1031772 T allele (odds ratio=1.40, P=0.018) were associated with a significantly higher risk of AHR. Haplotype analysis also detected significant association (P=0.006). Our findings suggest that SNPs located at the 3' downstream region of KCNS3 have a significant role in the etiology of AHR.

Adult↗

PubMed2005

Hepatic uptake of the novel antifungal agent caspofungin.

Caspofungin (CANCIDAS, a registered trademark of Merck & Co., Inc.) is a novel echinocandin antifungal agent used in the treatment of esophageal and invasive candidiases, invasive aspergillosis, and neutropenia. Available data suggest that the liver is a key organ responsible for caspofungin elimination in rodents and humans. Caspofungin is primarily eliminated by metabolic transformation; however, the rate of metabolism is slow. Accordingly, it was hypothesized that drug uptake transporters expressed on the basolateral domain of hepatocytes could significantly influence the extent of caspofungin uptake and subsequent elimination. In this study, experiments ranging from perfused rat livers to heterologous expression of individual hepatic uptake transporters were utilized to identify the transporter(s) responsible for the observed liver-specific uptake of this compound. Data from perfused rat liver studies were consistent with the presence of carrier-mediated caspofungin hepatic uptake, although this process appeared to be slow. To identify a relevant hepatic uptake transporter, we developed novel Tet-on HeLa cells expressing OATP1B1 (OATP-C, SLC21A6) and OATP1B3 (OATP8, SLC21A8), whose target gene can be overexpressed by the addition of doxycycline. A modest but statistically significant uptake of caspofungin was observed in cells overexpressing OATP1B1, but not OATP1B3. Taken together, these findings suggest that OATP1B1-mediated hepatic uptake may contribute to the overall elimination of this drug from the body.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Histone acetyltransferase activity of p300 enhances the activation of IL-18 promoter.

Interleukin-18 (IL-18), an important regulator of innate and acquired immune responses expressed from a variety of cell types, is a pleiotropic cytokine in the development of T helper type 1 (Thl) cells. The p300/CBP (CREB-binding protein) coactivator proteins are important histone acetyltransferases (HATs) that regulate the transcription of many genes. Whether p300/CBP play a role in the IL-18 expression has not been investigated previously. In this study, we analyzed the roles of p300 in the regulation of mouse IL-18 by using RT-PCR and a series of co-transfection studies. We showed that p300 had a stimulating effect on the endogenous IL-18 mRNA synthesis and on the activity of IL-18 p1 promoter. The results also showed that IL-18 p1 promoter activity was enhanced by p300 in a dose-dependent manner. Moreover, the p300-mediated activation function can be suppressed by the adenovirus E1A protein, which inhibits the HAT function of p300. Also, a mutation in p300 HAT region abolished the effect of p300 on IL-18 activation. These data further indicate that the acetylase activity of p300 was indispensable to its function. Furthermore, we found that p300 was able to enhance the effect of the transcription factor c-Fos on activation of the IL-18 promoter. Data presented in this paper implicate important roles of p300 in the transcriptional regulation of IL-18.

Acetyltransferases↗

PubMed2005

An extended hybrid density functional (X3LYP) with improved descriptions of nonbond interactions and thermodynamic properties of molecular systems.

We derive here the form for the exact exchange energy density for a density that decays with Gaussian-type behavior at long range. This functional is intermediate between the B88 and the PW91 exchange functionals. Using this modified functional to match the form expected for Gaussian densities, we propose the X3LYP extended functional. We find that X3LYP significantly outperforms Becke three parameter Lee-Yang-Parr (B3LYP) for describing van der Waals and hydrogen bond interactions, while performing slightly better than B3LYP for predicting heats of formation, ionization potentials, electron affinities, proton affinities, and total atomic energies as validated with the extended G2 set of atoms and molecules. Thus X3LYP greatly enlarges the field of applications for density functional theory. In particular the success of X3LYP in describing the water dimer (with R(e) and D(e) within the error bars of the most accurate determinations) makes it an excellent candidate for predicting accurate ligand-protein and ligand-DNA interactions.

Binding Sites↗

PubMed2005

Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous erosive arthritis.

OBJECTIVE: Erosion of cartilage and bone is a hallmark of rheumatoid arthritis (RA). This study was undertaken to explore the roles of hyperproliferating synovial fibroblasts and macrophages in abnormal osteoclast formation, using the recently described BXD2 mouse model of RA. METHODS: Cell distribution in the joints was analyzed by immunohistochemistry, using tartrate-resistant acid phosphatase (TRAP) staining to identify osteoclasts. To identify the defective cells in BXD2 mice, mouse synovial fibroblasts (MSFs) were cultured with bone marrow-derived macrophages. Osteoclast formation was assayed by TRAP staining and bone resorption pit assay, and the cytokine profiles of the MSFs and macrophages were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: In BXD2 mice, TRAP-positive osteoclasts were found at sites of active bone erosion, in close proximity to hyperproliferating synovial fibroblasts. On coculture, MSFs from BXD2 mice, but not C57BL/6 mice, produced high levels of RANKL messenger RNA, induced macrophages to form osteoclasts, and actively eroded bone slices, through a mechanism(s) that could be blocked by pretreatment with osteoprotegerin. Although macrophages from BXD2 mice expressed higher basal levels of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-6 than those from C57BL/6 mice, abnormal osteoclast formation was not due to enhanced sensitivity of the BXD2 mouse macrophages to RANKL. TNFalpha, produced by both BXD2 MSFs and BXD2 mouse macrophages, had a strong stimulatory effect on RANKL expression. CONCLUSION: BXD2 MSFs produce RANKL and induce the development of osteoclasts from macrophages. The enhanced production of RANKL is possibly due to autocrine stimulation, together with paracrine stimulation by factors produced by macrophages.

Animals↗

PubMed2005

Endovascular therapy for stanford type B aortic dissection in 102 cases.

OBJECTIVE: To share our experience of 102 cases of endovascular therapy for Stanford type B aortic dissection. METHODS: Multiple imaging diagnostic modalities were used preoperatively to obtain the anatomical parameters of the aortic dissection. Stent grafts were implanted using digital subtraction angiography and intravascular ultrasound guidance. Follow-up computed tomography angiography 1 week and 1 year postoperatively was used to evaluate treatment efficacy and reveal complications such as endoleak, migration and fracture of the stent graft. RESULTS: Clinical success was achieved in 101 cases (99.0%); one patient (1.0%) died within the perioperative period. Neither postoperative paraplegia nor conversion occurred. Endoleak occurred in 18 cases (17.6%). CONCLUSION: Endovascular therapy for Stanford type B aortic dissection is less invasive and leads to less severe complications and shorter hospital stay compared with traditional surgery. The short- and mid-term efficacy are persuasive, but further follow-up is required to determine long-term efficacy.

Adult↗

PubMed2005

A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients--a family-based association study.

Our recent study indicated that MTHFR C677T polymorphism may involve in genetic control of blood pressure response to treatment by benazepril, an ACE inhibitor. Currently, we proposed to further investigate whether short-term blood pressure response to benazepril, was modulated by haplotypes re-constructed from both C677T and A1298C polymorphisms in MTHFR gene. A total of 410 hypertensive patients recruited from 344 nuclear families were treated orally with benazepril at a daily dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. In addition, 689 family members of these patients were also genotyped. Among these patients, the frequency of MTHFR A1298C AA, AC and CC genotypes was 74.4%, 23.9%, and 1.7%, respectively. The frequency of MTHFR C677T CC, CT and TT genotypes was 23.7%, 51.2%, and 25.1%, respectively. Only three haplotypes, 677T-1298A (50.8%), 677C-1298A (35.7%), and 677C-1298C (13.5%) were re-constructed. Multivariate regression models with generalized estimating equation (GEE) correction detected that the individuals carrying one copy of haplotype 677C-1298C had significantly lower diastolic and systolic blood pressure response (DeltaDBP and DeltaSBP) to benazepril treatment (p= 0.003 and p =0.043, respectively), in comparison to those without haplotype 677C-1298C. The results of family-based association test further confirmed that haplotype 677C-1298C was more frequently transmitted in subjects with either lower residual of DeltaDBP or DeltaSBP. For residual of DeltaDBP, the p-values are 0.007 in an additive model and 0.005 in a dominant model. For residual of DeltaSBP, the p-values are 0.009 in an additive model and 0.006 in a dominant model. Our findings suggest that MTHFR 677C-1298C haplotype modulate blood pressure responsiveness to shortterm treatment of ACE inhibitor in Chinese essential hypertensive patients.

Adult↗