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Biomedical subjects

Jing Yuan

Publications and source records attributed to Jing Yuan.

At least 73 records · Page 4Linked to original sources

Multistep process through which adenoviral vector vaccine overcomes anergy to tumor-associated antigens.

Our goal in the present work was to characterize the multiple steps involved in overcoming the anergy that exists in tumor hosts to tumor-associated antigen (TAA). Our studies showed that the subcutaneous injection of the Ad-sig-TAA/ecdCD40L vector resulted in secretion of the TAA/ecdCD40L protein for at least 10 days from infected cells. Binding of the TAA/ecdCD40L protein to dendritic cells (DCs) resulted in the induction of CCR-7 chemokine receptor expression and cytokine release. This was followed by migration of the DCs to regional lymph nodes. Tetramer staining, enzyme-linked immunospot (ELISPOT) assay, and cytotoxicity assay all showed that the Ad-sig-TAA/ecdCD40L vector increased the levels of splenic CD8(+) T cells specific for the 2 TAAs (human MUC1 [hMUC1] and HPV E7) tested. Vaccination with the Ad-sighMUC1/ecdCD40L vector suppressed the growth of hMUC1 antigen-positive tumor cells in 100% of the test mice that were previously anergic to the hMUC1 antigen. These data suggest that Ad-sig-TAA-ecd/ecdCD40L vector injections may be of value in treating the many epithelial malignancies in which TAA-like hMUC1 is overexpressed.

Adenoviridae↗

High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene.

The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.

Acetyltransferases↗

Virtual sensing for broadband noise control in a lightly damped enclosure.

Available virtual sensing schemes either depend on assumptions that are valid for isolated frequencies, or require heavy online adaptations. A simple method is proposed here to predict the virtual signal exactly for broadband noise control in a lightly damped enclosure. The proposed method requires two physical sensors installed judiciously in a sound field to predict a virtual signal. The method is based on an exact mathematical relation between the virtual and physical sensors, which is valid for the entire frequency of interest. It is possible to use multiple sensor-pairs to reduce the sensitivity of the proposed method with respect to acoustic parameters, such as speed of sound or sensor mismatching. Experimental results are presented to verify the analytical results.

Acoustics↗

Role of Gab1 in UV-induced c-Jun NH2-terminal kinase activation and cell apoptosis.

Exposure of mammalian cells to UV irradiation leads to activation of the c-Jun NH(2)-terminal protein kinase (JNK) pathway, which is associated with cell apoptosis. However, the molecular mechanism for JNK activation by UV exposure is not fully understood. We show here an essential role of a multisubstrate adapter, Gab1, in this signaling cascade. Gab1-deficient mouse fibroblast cells were defective in induction of JNK activity by UV exposure or heat shock, and this defect was rescued by reintroduction of Gab1 into Gab1(-/-) cells. Consistently, Gab1(-/-) cells displayed reduced caspase 3 induction and apoptotic cell death in response to UV irradiation. Gab1 was constitutively complexed with JNK and became tyrosine phosphorylated in UV-irradiated cells. Genetic and pharmaceutical analyses suggest the involvement of c-Met and the Src family tyrosine kinases in mediating UV-induced Gab1 phosphorylation as well as JNK activation. In aggregate, these observations identify a new function of Gab1 in the response of mammalian cells to UV light.

Adaptor Proteins, Signal Transducing↗

A fast sequential image fractal coding approach based on optimal fuzzy clustering.

To reduce the coding time of the conventional method, a fast sequential image fractal compression algorithm was proposed on the basis of the principle of optimal fuzzy clustering (OFC) for an unsupervised sample set with the category number settled by the algorithm itself. We utilized the cost function defined by the OFC algorithm to obtain the best category number corresponding to the minimum value of the function. Firstly the Linde-Buzo-Gray (LBG) algorithm was realized to acquire a rough cluster of the domain pool. Then the optimal category number was obtained by implementing our algorithm with small computational cost. Finally the more precise category was gained and the detail of the reconstructed image efficiently preserved. As a global optimal algorithm, OFC not only helps LBG eliminate the local minima, but also effectively compensates for the arbitrary interference in hard clustering problem. Soft clustering of the domain blocks allows classified searches instead of global ones and takes less coding time, and therefore clearly outperforms to the classic method relying on reduction of the size of the domain pool by classification. In computer simulation, OFC-based algorithm for the fractal coding scheme achieved excellent performance. For some standard and sequential medical images, the results denoted that the encoding speed was improved by about 5 folds without affecting the signal-to-noise ratio and compression ratio, and the quality of the reconstructed image could be better retained.

Algorithms↗

Novel peptidomimetic inhibitors of signal transducer and activator of transcription 3 dimerization and biological activity.

The critical role of signal transducer and activator of transcription 3 (Stat3) in the growth and survival of human tumor cells identifies it as a promising target for cancer drug discovery. We previously identified a Stat3 SH2 domain-binding phosphopeptide, PY*LKTK, and its tripeptide derivatives, PY*L and AY*L (where Y* represents phosphotyrosine), which inhibit Stat3 biochemical activity and biological function. Here, we report novel peptidomimetic compounds based on PY*L (or AY*L) with substitution of the Y-1 residue by benzyl, pyridyl, or pyrazinyl derivatives that are selective and greater than 5-fold more potent in disrupting Stat3 activity in vitro than lead tripeptides. The biological activities of these derivatives mirror that originally observed for peptides. In this context, the representative peptidomimetic ISS 610 with 4-cyanobenzoate substitution inhibits constitutive Stat3 activity in Src-transformed mouse fibroblasts and human breast and lung carcinoma cells. This effect is not evident with the non-phosphorylated counterpart, ISS 610NP, consistent with interaction of peptidomimetics with the SH2 domain of Stat3. Moreover, ISS 610 induces cell growth inhibition and apoptosis of Src-transformed fibroblasts that contain persistently active Stat3. We present the first report of a peptidomimetic approach to design of small-molecule inhibitors of Stat3 that are also among the first examples of disruptors of transcription factor dimerization with the potential for novel cancer therapy.

Agar↗

Induction, expression and maintenance of cytochrome P450 isoforms in long-term cultures of primary human hepatocytes.

Within the past decade, tremendous progress has been made in the isolation and culture of human hepatocytes for drug metabolism and toxicology, which could potentially reduce the number of animal experiments performed. However, human hepatocyte cultures are still not widely used for preclinical drug testing, partly due to inconsistent supply and quality of human tissue. Thus, the aim of this study was to evaluate primary cultured human hepatocytes from different patients over a study period of 14 days, by assays that characterise cell quality and function. We found urea production and albumin synthesis in all cell cultures over at least 7 days. Cytochrome P4501A2, CYP2D6, and CYP3A4 protein expression was demonstrated by Western Blot analysis and CYP1A1/2 and CYP3A4 induction by 3-methylcholantrene, phenobarbital or rifampicin over 14 days. In addition, we saw that UDP-glucoronyltransferase activity was preserved in human hepatocytes over 2 weeks. In conclusion, we could show that primary human hepatocytes isolated from discarded liver tissue can consistently be kept in culture over a long time period and are therefore well suited for preclinical drug testing.

Albumins↗

[Complications related to permanent deep venous catheterization using dual lumen hemodialysis catheter].

OBJECTIVE: To observe the incidence of long-term venous indwelling catheter related complications in hemodialysis patients and to report our clinical approach to the complications. METHODS: A hundred eleven hemodialysis patients was prospectively studied from Jan. 2001 to Mar. 2003, in whom the venous indwelling catheter had been in place for more than 6 months. Catheter related complications were observed over a total period of 1090 patients months, with a mean period of 9.8 months (6 - 27 months). RESULTS: The incidence of hematoma was 8.1% (9/111), and that of catheter malposition was 4.5%. There was no hemothorax, pneumothorax, air embolism or veinous laceration. Six episodes of catheter related infection were observed during the observation, with an incidence of 5.4%; two cases with bacterial infection were successfully treated; while among the 4 cases with fungal infection, one was successfully treated and catheters were removed in other 3 cases for uncontrolled infection. The incidence of catheter thrombosis was 18.9% (21/111) and the catheter had been used for a mean period of 36 days (6 - 725 days) from placement to thrombosis. Catheter patency was restored in 95.2% (20/21) by urokinase infusion. Recurrent thrombosis occurred in 18 of 20 catheters (90.0%), of which 5 worked functionally following anti-platelet therapy and 13 had recurrent thrombosis. Following anticoagulation by warfarin, 9 became functional (69.2%), but the other 4 cases turned to other vascular access. Urokinase infusion followed by anticoagulation had prolonged the mean catheter life-time for 6 months (3 - 18 months). CONCLUSION: Cuffed dual lumen catheter as permanent access is safe and effective. Catheter thrombosis is the most common complication. Urokinase infusion followed by anticoagulation can significantly prolong the catheter life-time.

Adolescent↗

[Clinical features of 23 cases of AIDS complicated by tuberculosis].

OBJECTIVE: To discuss the clinical features, treatment and prognosis of patients with AIDS complicated by tuberculosis(TB). METHODS: The clinical features of 23 patients with AIDS complicated by tuberculosis admitted from 1997 to July 2004 were retrospectively analyzed. RESULTS: Of the 23 patients, most (94.3%) were young or middle-aged, and 11 (47.8%) died within half a year. The main HIV transmission was via sexual contact in 15 (65.2%) patients. Loss of body weight by 5 - 15 kg was present in all patients, cough for over 1 month in 15 (65.2%), and multiple opportunistic infections were complicated in most cases. Out of the 23 cases, 14 (60.9%) showed only pulmonary TB, and 8 (34.8%) showed lymph node TB. In 12 cases with infiltrated pulmonary TB, X-ray showed bilateral infiltration and no cavity formation was found. Slightly positive PPD test was found in 2 (8.7%) cases, and positive acid-fast bacilli was detected in sputum in 1 case (4.4%). The pre-treatment CD(4)(+) cell number in 23 patients was much lower than that in AIDS patients without complicated TB (P < 0.05). The pre-treatment CD(4)(+) cell number in patients died shortly after diagnosis was much lower than that in survived patients (P < 0.05). The HIV RNA level in the 23 patients was much higher than that in patients without complication of TB (P < 0.05). The mortality in patients treated with therapy against both TB and HIV was much lower than that in patients untreated or treated only with anti-TB therapy (P < 0.05). CONCLUSIONS: For patients with AIDS complicated by TB, the high negative rate in PPD test and the atypical chest X-ray manifestations are common. However, lymph node TB is quite common with high mortality. The pre-treatment CD(4)(+) level decreases significantly, and is associated with mortality. The TB bacilli may accelerate HIV virus duplication. It is suggested that the patients be treated with a combination of anti-TB and anti-HIV therapies.

Acquired Immunodeficiency Syndrome↗

Chiral molecular assemblies from a novel achiral amphiphilic 2-(heptadecyl) naphtha[2,3]imidazole through interfacial coordination.

A novel amphiphilic compound 2-(heptadecyl) naphtha[2,3]imidazole (NpImC17) was synthesized, and its coordination with AgNO(3) in situ in the monolayer at the air/water interface and ex situ in the Langmuir-Blodgett (LB) film on solid substrate has been investigated. It has been found that interfacial coordination between NpImC17 and Ag(I) ion occurred both in the monolayer and in the LB film. It is interesting to note that the Ag(I)-coordinated ultrathin film became chiral although the ligand itself is achiral. It was suggested that the chirality of the Ag(I)-coordinated LB film was developed due to the formation of a helical coordination polymer through the interfacial coordination. To the best of our knowledge, this is the first report on the formation of chiral monolayer and LB films from an achiral molecule through interfacial coordination.

Journal Article↗

Regulation of the cyclin D3 promoter by E2F1.

We have previously demonstrated that ectopic expression of E2F1 is sufficient to drive quiescent cells into S phase and that E2F1 expression can contribute to oncogenic transformation. Key target genes in this process include master regulators of the cell cycle, such as cyclin E, which regulates G(1) progression, and cyclin A, which is required for the initiation of DNA synthesis. In the present work, we present novel evidence that a second G(1) cyclin, cyclin D3, is also potently activated by E2F1. First, an estrogen receptor-E2F1 fusion protein (ER-E2F1) potently activates the endogenous cyclin D3 mRNA upon treatment with 4-hydroxytamoxifen, which induces nuclear accumulation of the otherwise cytosolic fusion protein. Furthermore, trans-activation of cyclin D3 by ER-E2F1 occurs even in the presence of the protein synthesis inhibitor cycloheximide and thus appears direct. Second, all of the growth-stimulatory members of the E2F family (E2F1, -2, and -3A) potently activate a cyclin D3 promoter reporter, whereas growth-restraining members of the family (E2F4, -5, and -6) have little effect. Third, recombinant E2F1 binds with high affinity to the cyclin D3 promoter in vitro. Fourth, chromatin immunoprecipitation assays demonstrate that endogenous E2F1 is associated with the cyclin D3 promoter in vivo. Finally, mapping experiments localize the essential E2F regulatory element of the cyclin D3 promoter to a noncanonical E2F site in the promoter between nucleotides -143 and -135 relative to the initiating methionine codon. We conclude that in addition to cyclins E and A, E2F family members can also activate one member of the D-type cyclins, further contributing to the ability of the stimulatory E2F family members to drive cellular proliferation.

Cell Cycle Proteins↗

Construction and characterization of a novel 13.34-fold chicken bacterial artificial chromosome library.

A chicken bacterial artificial chromosome (BAC) library consisting of 138,240 clones was constructed in vector pBeloBAC11 with genomic DNA isolated from female white-silk chicken. An average insert size of 118 kb was estimated from 452 randomly isolated clones, which indicate the library to be approximate 13.34-fold genome coverage. For the demonstration of the probability to pick out any unique genes or DNA markers from the library, 8 single-copy genes were screened out and the positive clones were yielded between 2 and 15 with an average of 11.125, in agreement with the estimated high genomic coverage of this library. Positive superpools were obtained for 40 microsatellite markers selected from different regions of chicken genome. The number of positive superpools for each marker varies from 1 to 15 with an average of 9.475.

Animals↗

Causal impedance matching for broadband hybrid noise absorption.

The complementary strengths and weaknesses of passive and active noise control (ANC) methods have motivated many researchers to develop hybrid noise absorbers that integrate both control strategies. The impedance matching technique (IMT) is the most effective for such a purpose. An unsolved problem with available IMT schemes is the a priori reference signal that limits IMT applications. This study proposes the use of the forward wave, available by the two-microphone method, as the reference signal. Due to inevitable errors in wave separation and inlet reflection of the control signal, the absorber becomes a feedback system. A simple and stable ANC is developed for impedance matching without the a priori reference signal. The proposed absorber has an absorption coefficient of 0.9 or above in a frequency range of 60-850 Hz. It is stable in the presence of sensor mismatch and robust with respect to significant variation of inlet boundary conditions.

Journal Article↗

Improving robustness of active noise control in ducts.

A robust active noise controller (ANC) is proposed here for finite ducts. While the H(infinity) control theory provides theoretical ground and numerical algorithms to design robust controllers, it is important for an engineer to design and formulate a robust controller so that the objective is more achievable and the H(infinity) constraints less restrictive without sacrificing robustness. A new robust ANC is designed this way with an extra actuator to improve achievable performance and introduce more degrees of freedom to controller parameters. The new strategy relaxes H(infinity) constraints without sacrificing robustness and enables the ANC to tolerate a wide variety of errors and uncertainties including truncation errors between a finite model and an infinite field. Theoretical analysis, numerical examples, and experimental results are presented to demonstrate the improved performance of the proposed ANC when subject to a certain level of uncertainties in a duct.

Journal Article↗

[Potential molecular mechanism of multiple organ dysfunction syndrome induced by hemorrhage and endotoxin].

OBJECTIVE: To investigate the possible molecular mechanism of multiple organ dysfunction syndrome (MODS) associated with hemorrhagic shock followed by resuscitation and endotoxin. METHODS: A rabbit model of MODS after hemorrhagic shock followed by resuscitation and endotoxin was used in this study. The expression of I-kappaB kinase-beta (IKK-beta), the activity of nuclear factor-kappaB (NF-kappaB) in macrophage (PAM) and Kupffer cell (KC), the concentration of tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant were measured by in situ hybridization (ISH), electrophoretic mobility shift assay (EMSA) and enzyme linked immunoadsorbent assay (ELISA), respectively. Then the blood gas, biochemistrical and pathological changes in lungs, liver and intestines were examined in each groups. RESULTS: In the MODS group, the expression of IKK-beta mRNA (0.15+/-0.03, 0.17+/-0.04), the activity of NF-kappaB (1.49+/-0.30, 1.72+/-0.36) and the levels of TNF-alpha[(279.74+/-25.91)ng/L, (300.05+/-30.86)ng/L] in PAM and KCs were significantly higher than those of normal controls[IKK-beta mRNA 0.03+/-0.01 and 0.02+/-0.01; NF-kappaB 0.25+/-0.06 and 0.31+/-0.10, TNF-alpha (137.33+/-6.09)ng/L and (134.85+/-12.09)ng/L, respectively, all P<0.01]. Also, the contents of blood urea nitrogen (BUN), alanine aminotransferase (ALT) in plasma significantly increased, the arterial oxygen partial pressure decreased, and the severity of organ damages in lungs, liver as well as intestines increased following MODS. CONCLUSION: The IKK-beta expression, NF-kappaB activation and cytokine release may play important roles in the pathogenesis of acute lung injury and MODS.

Animals↗

[Effect and significance of anisodamine on IkappaB kinase-beta in Kupffer cells following hemorrhagic shock].

OBJECTIVE: To investigate the possible role of IkappaB kinase-beta (IKK-beta), the pathogenesis of hepatic injury induced by resuscitation of hemorrhagic shock and endotoxin, and to evaluate the preventive effect of anisodamine (654-2). METHODS: Twenty-seven rabbits were randomly divided into the normal group, hemorrhagic shock plus endotoxin group and 654-2 treatment group. The expression of IKK-beta, activity of the nuclear factor-kappaB (NF-kappaB) in Kupffer cells (KC) and the concentration of tumor necrosis factor-alpha (TNF-alpha) in the culture supernatant were measured by in situ hybridization (ISH), electrophoretic mobility shift assay (EMSA) and enzyme linked immunoadsorbent analysis (ELISA), respectively. The pathological changes in the hepatic tissue were examined with light microscope. RESULTS: Compared with the normal group, the expression of IKK-beta (0.21+/-0.03), the activity of NF-kappaB (2.29+/-0.25) in KC, and the level of TNF-alpha[(560.21+/-31.04) ng/L] in the culture supernatant of KC were obviously increased after hemorrhagic shock and endotoxin(all P<0.01 ). 654-2 treatment could significantly inhibit the expression of IKK-beta (0.14+/-0.03) and the activity of NF-kappaB (1.35+/-0.17) in KC, decrease the content of TNF-alpha [(300.79+/-23.47) ng/L] in the culture supernatant of KC in rabbits with hemorrhagic shock plus endotoxin challenge (all P<0.01 ),and alleviate hepatic injury as observed by histological examination. CONCLUSION: IKK-beta expression in KC could be enhanced after hemorrhagic shock and endotoxin, and it might play an important role in the development and progression of hepatic injury following hemorrhagic shock and endotoxin. 654-2 could inhibit IKK-beta expression, decrease NF-kappaB activation and cytokine secretion in KC after hemorrhagic shock followed by resuscitation and endotoxin. The inhibition of IKK-beta expression might be a protective mechanism for hepatic injury.

Animals↗

[Effects of polymixin B on I-kappaB kinase mRNA expression in lipopolysaccharide- induced pulmonary alveolar macrophages].

OBJECTIVE: To investigate effects of polymixin B (PMB) on I-kappaB kinase(IKK-beta), inhibitor protein(IkappaB-alpha) and nuclear factor-kappa B(NF-kappaB) in lipopolysaccharide(LPS)-induced pulmonary alveolar macrophages (PAM), and explore the anti-inflammatory mechanism of PMB. METHODS: PAM from rats collected by bronchoalveolar lavage was cultured and divided into three groups. In the control group, PAM was not stimulated with LPS and not treated with PMB. In the LPS stimulated group, PAM was stimulated with LPS. In the PMB treated group, PAM was pretreated with PMB half an hour prior to LPS stimulation. The expression of IKK-beta mRNA, level of IkappaB-alpha and the activity of NF-kappaB in PAM were measured by in situ hybridization(ISH), enzyme linked immunoadsorbent assay (ELISA) and electrophoretic mobility shift assay(EMSA), respectively. RESULTS: In the LPS stimulated group, the expression of IKK-beta mRNA (0.147+/-0.015) and activity of NF-kappaB (0.828+/-0.019) in PAM significantly increased, whereas levels of IkappaB-alpha (0.228+/-0.021) decreased (all P<0.01) in PMB treated groups. The expression of IKK-beta mRNA (0.112+/-0.022) and activity of NF-kappaB (0.358+/-0.011) were down-regulated while level of IkappaB-alpha (0.477+/-0.016) was up-regulated(P<0.01). CONCLUSION: LPS might induce expression of IKK-beta mRNA, degradation of IkappaB-alpha and activation of NF-kappaB PMB could inhibit the expression of IKK-beta, degradation of IkappaB-alpha and activation of NF-kappaB, showing marked anti-inflammatory property.

Animals↗