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Biomedical subjects

Qi Shen

Publications and source records attributed to Qi Shen.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Pulmonary fungal infection in malignant hematological diseases: an analysis of 14 cases].

The objective of this study was to evaluate the etiological factors, diagnosis and therapy of pulmonary fungal infection in hematological malignancies, 14 cases of malignant hematological disease with pulmonary fungal infection were collected and analyzed. The results showed that 11 out of 14 cases had the respiratory manifestations, sputum was sticky and difficult to be expectorated in 7 cases, X rays in chests showed shadows with features of stigma and sheet in 11 cases, Candida albicans and aspergillus infection were observed in 10 and 2 cases respectively, the numbers of neutrophil were below 0.5 x 10(9)/L in 8 cases and below 1.0 x 10(9)/L in 3 cases respectively, fluconazole was used for 12 cases and clinical symptoms of 11 cases were improved within two weeks. In conclusion, the occurrence of pulmonary fungal infection in malignant hematological diseases is associated with intensive chemotherapy, decrease of neutrophil counts and using of broad-spectrum antibiotics, the diagnosis at early stage is difficult and clinicians should pay more attention to its clinical and laboratory examinations, and give them therapy in time.

Adolescent↗
PubMed2004

Hybridized particle swarm algorithm for adaptive structure training of multilayer feed-forward neural network: QSAR studies of bioactivity of organic compounds.

The multilayer feed-forward ANN is an important modeling technique used in QSAR studying. The training of ANN is usually carried out only to optimize the weights of the neural network and without paying attention to the network topology. Some other strategies used to train ANN are, first, to discover an optimum structure of the network, and then to find weights for an already defined structure. These methods tend to converge to local optima, and may also lead to overfitting. In this article, a hybridized particle swarm optimization (PSO) approach was applied to the neural network structure training (HPSONN). The continuous version of PSO was used for the weight training of ANN, and the modified discrete PSO was applied to find appropriate the network architecture. The network structure and connectivity are trained simultaneously. The two versions of PSO can jointly search the global optimal ANN architecture and weights. A new objective function is formulated to determine the appropriate network architecture and optimum value of the weights. The proposed HPSONN algorithm was used to predict carcinogenic potency of aromatic amines and biological activity of a series of distamycin and distamycin-like derivatives. The results were compared to those obtained by PSO and GA training in which the network architecture was kept fixed. The comparison demonstrated that the HPSONN is a useful tool for training ANN, which converges quickly towards the optimal position, and can avoid overfitting in some extent.

Journal Article↗
PubMed2004

RNA-mediated gene silencing of the RON receptor tyrosine kinase alters oncogenic phenotypes of human colorectal carcinoma cells.

Altered expression of receptor tyrosine kinases contributes to tumorigenic behaviors of epithelial cancers. In this study, the pathogenic roles of receptor tyrosine kinase RON (recepteur d'origine nantais) in regulating oncogenic phenotypes in colorectal epithelial cells were studied. Increased expression of RON and its variants resulted in colony formation and motile activities of colonic epithelial AA/C1 cells as evident in soft-agar and migration assays, respectively. These results suggest that overexpression of wild-type RON mediates the transformed phenotypes in immortalized colon epithelial cells. In colorectal cancer cells (HT-29, HCT116, and SW620) that naturally express RON, the RON gene expression was silenced by RNA interference. The introduction of RON-specific small interfering (si) RNA significantly affected cancer cell proliferation, motility, and led to increased apoptotic cell death. Focus-forming activities and anchorage-independent growth of colon cancer cells were also dramatically reduced. Moreover, it was demonstrated in tumor growth assays that silencing RON gene expression significantly reduces tumorigenic activities of SW620 cells in vivo. By analysing signaling proteins involved in colon carcinogenesis, we found that the effect of RON-specific siRNA is associated with diminished expression of beta-catenin, a critical component in the Wnt signaling pathway. Taken together, our results demonstrate that altered expression of RON in colon cancer cells is required to maintain tumorigenic phenotypes. Thus, silencing RON gene expression could have potential to reverse malignant activities of colon tumors in vivo.

Carcinoma↗
PubMed2004

A first oxalamidino complex of samarium via reduction-coupling of carbodiimine: synthesis and molecular structure of [eta4-C2(NR)4][(MeC5H4)2Sm(HMPA)]2.2THF (R = Pr i, Cy).

Treatment of the THF solution of (MeC5H4)2Sm(THF) with an equivalent of carbodiimine [RN=C=NR](R = Pr(i) or Cy; Cy = cyclohexyl) in the presence of an equivalent of hexamethylphosphoric triamide (HMPA) at room temperature gives, via a reduction-coupling reaction of carbodiimine, the corresponding bimetallic oxalamidino complex of samarium [eta4-C2(NR)4][(MeC5H4)2Sm(HMPA)]2.2THF.

Journal Article↗
PubMed2004

Activation of the RON receptor tyrosine kinase attenuates transforming growth factor-beta1-induced apoptotic death and promotes phenotypic changes in mouse intestinal epithelial cells.

The RON (recepteur d'origine nantais) receptor belongs to the MET proto-oncogene family that is implicated in the oncogenesis of the gastrointestinal epithelium. The present study aimed to determine the role of RON in regulating epithelial phenotypes in response to transforming growth factor (TGF)-beta1. Expression and activation of RON in SV40-immortalized mouse intestinal epithelial MODE-K cells result in reduction of cellular sensitivities towards apoptotic signals elicited by TGF-beta1. This effect is dependent on RON expression and phosphorylation that inhibit the TGF-beta1-induced activation of caspase-3 and truncation of BAD. Among cellular signaling components, the activation of MAP kinase is critical in the RON-mediated inhibitory effect. PD98059, a specific MAP kinase inhibitor, prevented RON-mediated anti-apoptotic activities. PD98059 also prevented the inhibitory effect of RON on TGF-beta1-induced cleavage of caspase-3 and BAD. By protecting cells from apoptotic death, activated RON collaborates with TGF-beta1 in the induction of cell morphological changes with decreased E-cadherin expression and increased migration and morphogenesis. Thus, RON expression and activation modulate phenotypes of gastrointestinal epithelial cells in response to TGF-beta1 with reduced sensitivity to apoptosis and increased migration. These activities might represent a mechanism by which RON activation increases tumorigenic activities and facilitates the progression of transformed epithelial cells towards malignancy.

Animals↗
PubMed2004

QSAR analysis of cyclooxygenase inhibitor using particle swarm optimization and multiple linear regression.

Quantitative structure-activity relationship (QSAR) models of inhibiting action of some diarylimidazole derivatives on cylcooxygenase (COX) enzyme were constructed using modified particle swarm optimization (PSO) method. As a comparison to this method, the genetic algorithm (GA) was also tested. It has been demonstrated that the modified PSO is a useful tool for variable selection comparable to GA and even superior to GA. QSAR models are constructed separately for COX-2 inhibitory activity and selectivity of COX-2 inhibition over COX-1. The spatial descriptors play a key role in the compounds' activity and selectivity to COX-2, especially Jurs descriptors. Polar interactions are the principal binding strength between compounds and COX-2 enzyme. In addition, the aqueous desolvation free energy (FH2O) value of substituent will affect the COX-2 inhibitory activity, while the charge distribution can affect the selectivity to COX-2.

Cyclooxygenase Inhibitors↗
PubMed2004

Collaborative activities of macrophage-stimulating protein and transforming growth factor-beta1 in induction of epithelial to mesenchymal transition: roles of the RON receptor tyrosine kinase.

Epithelial to mesenchymal transition (EMT) is a process occurring during embryonic development and cancer progression. Using recepteur d'origine nantais (RON)-expressing epithelial cells as a model, we showed that RON activation causes spindle-shaped morphology with increased cell motilities. These activities resemble those observed in EMT induced by transforming growth factor (TGF)-beta1 or by Ras-Raf signaling. By immunofluorescent and Western blot analyses, we found that constitutive RON expression results in diminished expression of E-cadherin, redistribution of beta-catenin, reorganization of actin cytoskeleton, and increased expression of vimentin, a mesenchymal filament. RON expression is also essential for TGF-beta1-induced expression of alpha-smooth muscle actin (alpha-SMA), a specialized mesenchymal marker. In the study of signaling pathways responsible for RON-mediated EMT, it was found that PD98059, a MAP kinase inhibitor, blocks the collaborative activities of RON and TGF-beta1 in induction of alpha-SMA expression and restores epithelial cells to their original morphology. Moreover, we showed that RON expression increases Smad2 gene promoter activities and protein expression, which significantly lowers TGF-beta1 threshold for EMT induction. These results suggest that persistent RON expression and activation cause the loss of epithelial phenotypes. These changes, collaborating with TGF-beta1 signaling, could play a critical role in epithelial transdifferentiation towards invasiveness and metastasis of certain cancers.

Actins↗
PubMed2004

Effects of rexinoids on glucose transport and insulin-mediated signaling in skeletal muscles of diabetic (db/db) mice.

Rexinoids and thiazolidinediones (TZDs) are two classes of nuclear receptor ligands that induce insulin sensitization in diabetic rodents. TZDs are peroxisome proliferator-activated receptor gamma (PPARgamma) activators, whereas rexinoids are selective ligands for the retinoid X receptors (RXRs). Activation of both the insulin receptor substrates (IRSs)/Akt and the c-Cbl-associated protein (CAP)/c-Cbl pathways are important in regulating insulin-stimulated glucose transport. We have compared the effects of a rexinoid (LG268) and a TZD (rosiglitazone) on these two signal pathways in skeletal muscle of diabetic (db/db) mice. The results we have obtained show that treatment of db/db mice with either LG268 or rosiglitazone for 2 weeks results in a significant increase in insulin-stimulated glucose transport activity in skeletal muscle. Treatment with LG268 increases insulin-stimulated IRS-1 tyrosine phosphorylation and Akt phosphorylation in skeletal muscle without affecting the activity of the CAP/c-Cbl pathway. In contrast, rosiglitazone increases the levels of CAP expression and insulin-stimulated c-Cbl phosphorylation without affecting the IRS-1/Akt pathway. The effects of LG268 on the IRS-1/Akt pathway were associated with a decrease in the level of IRS-1 Ser(307) phosphorylation. Taken together, these data suggest that rexinoids improve insulin sensitivity via changes in skeletal muscle metabolism that are distinct from those induced by TZDs. Rexinoids represent a novel class of insulin sensitizers with potential applications in the treatment of insulin resistance.

Acyl Coenzyme A↗
PubMed2004

Novel lanthanide(II) complexes supported by carbon-bridged biphenolate ligands: synthesis, structure and catalytic activity.

[Ln[N(SiMe3)2]2(THF)2](Ln = Sm, Yb) reacts with 1 equiv. of carbon-bridged biphenols, 2,2'-methylene-bis(6-tert-butyl-4-methylphenol)(L1H2) or 2,2'-ethylidene-bis(4,6-di-tert-butylphenol)(L2H2), in toluene to give the novel aryloxide lanthanide(II) complexes [[LnL1(THF)n]2](Ln = Sm, n = 3 (1); Ln = Yb, n = 2 (2)) and [[LnL2(THF)3]2](Ln = Sm (5); Ln = Yb (6)) in quantitative yield, respectively. Addition of 2 equiv. of hexamethylphosphoric triamide (HMPA) to a tetrahydrofuran (THF) solution of 1, 2 and 5 affords the corresponding HMPA-coordinated complexes, [[LnL1(THF)m(HMPA)n]2(THF)y](Ln = Sm, n = 2, m = 0, y = 2 (3); Ln = Yb, m = 1, n = 1, y = 6 (4)) and [[SmL2(HMPA)2]2](7) in excellent yields. The single-crystal structural analyses of 3, 4 and 7 revealed that these aryloxide lanthanide(II) complexes are dimeric with two Ln-O bridges. The coordination geometry of each lanthanide metal can be best described as a distorted trigonal bipyramid. Complexes 1-3, 5 and 7 can catalyze the ring-opening polymerization of epsilon-caprolactone (epsilon-CL), and 1-3, along with 5 show moderate activity for the ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) and the copolymerization of epsilon-CL and DTC to give random copolymers with high molecular weights and relatively narrow molecular weight distributions..

Journal Article↗
PubMed2004

Insulin expression in livers of diabetic mice mediated by hydrodynamics-based administration.

AIM: Transfer and expression of insulin gene in vivo are an alternative strategy to improve glycemic control in type 1 diabetes. Hydrodynamics-based procedure has been proved to be very efficient to transfer naked DNA to mouse livers. The basal hepatic insulin production mediated by this rapid tail vein injection was studied to determine its effect on the resumption of glycemic control in type 1 diabetic mice. METHODS: Engineered insulin cDNA was inserted into plasmid vectors under a CMV promoter, and transferred into STZ induced diabetic mice by hydrodynamic procedure. Glucose levels, body weight of treated mice, insulin levels, immunohistology of the liver, and quantity of insulin mRNA in the liver were assayed to identify the improvement of hyperglycemic complication after plasmid administration. Sleeping Beauty, a transposon system, was also used to prolong the insulin expression in the liver. RESULTS: After plasmid administration, Plasma insulin was significantly increased in the diabetic mice and the livers were insulin-positive by immunostaining. At the same time the hyperglycemic complication was improved. The blood glucose levels of mice were reduced to normal. Glucose tolerance of the treated diabetic mice was improved. Body weight loss was also ameliorated. The rapid tail vein injection did not cause any fatal result. CONCLUSION: Our results suggested that insulin gene could be efficiently transferred into the livers of diabetic mice via rapid tail vein injection and it resulted in high level of insulin expression. The basal hepatic insulin production mediated by hydrodynamics-based administration improved the glycemic control in type 1 diabetes dramatically and ameliorated diabetic syndromes. Hydrodynamics-based administration offers a simple and efficient way in the study of gene therapy for type 1 diabetes.

Animals↗
PubMed2004

Modified particle swarm optimization algorithm for variable selection in MLR and PLS modeling: QSAR studies of antagonism of angiotensin II antagonists.

A version of modified particle swarm optimization (PSO) algorithm has been proposed. The PSO algorithm has been modified to adopt to the discrete combinatorial optimization problem and reduce the probability of sinking into local optima. In the modified PSO algorithm, the velocity represents the probability of element in each particle taking value 1 or 0. The modified discrete PSO algorithm is proposed to select variables in MLR and PLS modeling and to predict antagonism of angiotensin II antagonists. The modified C(p) is employed as fitness function. The results were compared to those obtained by GAs. Experimental results have demonstrated that the modified PSO is a useful tool for variable selection which converges quickly towards the optimal position.

Algorithms↗
PubMed2004

Enhancement of naked FIX minigene expression by chloroquine in mice.

AIM: To study the effect of chloroquine on the expression of human clotting factor IX (hFIX) in mice. METHODS: Hydrodynamics-based naked DNA plasmid administration was performed by tail vein injection of 10 microg of pCMV- hFIX and chloroquine (0, 100, 200, and 500 micromol/L) in 2.2 mL of Ringer's solution within 6-7 s, the level and stability of hFIX expression, liver damage and toxicity were then examined. RESULTS: The maximum expression of hFIX level was 4.4+/-1.8 mg/L at 8 h after injection, 9.7+/-1.6 mg/L at 24 h only existed in 200 micromol/L chloroquine-treated animals, which is 3-4 fold higher than that of control (P<0.01). There is no significant difference observed among all the treated groups, 3 d later. Transaminase level and liver histological study showed the damage of liver was not related to chloroquine (P>0.05). CONCLUSION: Chloroquine can enhance and sustain exogenous gene expression in vivo without side effect under our experimental conditions.

Alanine Transaminase↗
PubMed2003

Genomic characterization and regulation of CYP3a13: role of xenobiotics and nuclear receptors.

We report that CYP3a13 gene, located on mouse chromosome 5, spans 27.5 Kb and contains 13 exons. The transcription start site is 35 bp upstream of the coding region and results in a 109 bp 5' untranslated region. CYP3a13 promoter shows putative binding sites for retinoid X receptor, pregnane X receptor, and estrogen receptor. CYP3a13 shows a broad tissue distribution with predominant expression in liver. Although CYP3a13 shares 92% nucleotide identity with the female-specific rat CYP3A9, its expression does not exhibit sexual dimorphism. Ligand activation of peroxisomal proliferator-activated receptor-gamma and retinoid X receptor inhibit expression of CYP3a13 at the transcription level in a tissue-specific manner. Another novel finding is hepatic induction of CYP3a13 by dexamethasone occurring only in pregnane X receptor null mice. We also report that pregnane X receptor is essential to maintain robust in vivo basal levels of CYP3a13 in contrast to CYP3a11. CYP3a13 protein expressed in vitro can metabolize clinically active drugs ethylmorphine and erythromycin, as well as benzphetamine. We conclude that CYP3a13 is regulated differentially by various nuclear receptors. In humans this may lead to altered drug metabolism, as many of the newly synthesized ligands/drugs targeted toward these nuclear receptors could influence CYP3A gene expression.

Animals↗
PubMed2003

Novel synthesis of 1-aroyl-3-aryl-4-substituted imidazole-2-thiones.

[reaction: see text] An efficient route to 1-aroyl-3-aryl-4-substituted imidazole-2-thiones (2, 4-6) has been developed. The methodology involves the cyclization of 1-aroyl-3-arylthioureas with a variety of carbonyl compounds bearing alpha-H in the presence of bromine and triethylamine.

Anti-HIV Agents↗
PubMed2003

Quantitative structure-activity relationships (QSAR): studies of inhibitors of tyrosine kinase.

A quantitative structure-activity relationship (QSAR) study of the 1-phenylbenzimidazoles as inhibitors of the platelet-derived growth factor receptor (PDGFR) was performed. Some new electronic parameters Q(o), Q(m) and Q(p) are suggested for characterizing the effect of substituents. Many other descriptors are also used which are selected by evolution algorithm (EA) using modified Cp as objective function proposed by the present authors. The descriptor Q(m) is shown to be an important variable to express effect of substituents. The variable selection shows that spatial descriptors are most important variables revealing important properties of the inhibitors. Electron-releasing substitutes at 5-position and the absence of bulky groups at 4,7-positions of the parent structure can enhance inhibitor activity. Principal component analysis is performed to classify this series of compounds.

Benzimidazoles↗
PubMed2003

[Analysis of clinical application for various types of esophageal stents made in China].

BACKGROUND & OBJECTIVE: Dysphagia is the main clinical symptom of the patients with esophageal carcinoma. The stent placement in esophagus is an effective method to resolve dysphagia.There are many types of stents. Through comparing observation of the stents made in China, which is the stainless steel "Z" stent, the Ni-Ti wire mesh-like stent, and the covered or uncovered-stent, the authors analyzed the clinical application of various types of esophageal stents in the treatment of malignant esophageal stricture. METHODS: The various types of esophageal stents were implanted into 40 patients with esophageal carcinoma. 13 cases for stainless steel "Z" stents, 27 cases for Ni-Ti wire mesh-like stents(24 cases were the covered stents and 16 cases were uncovered). All the patients were not operated with the dilation of balloon before stent placement. RESULTS: The esophageal stents were successfully implanted into 40 patients without complication of operation. Stainless steel "Z" stent were all dilated immediately at the time of operation, and all the 13 patients had obvious intra-breastbone pain after operation, which lasted 10-20 days. Although Ni-Ti wire mesh-like stents could not dilate completely in operation, all these can be dilated completely after 1 to 3 days; nine cases of them had obvious intra-breastbone pain, which lasted 3-5 days. In all these, 7 cases were the covered-stents and 2 cases uncovered. In 9 cases, tracheoesophageal fistulas were blocked completely. There was barium sulphate retention between the covered-stent implanted to the patients without tracheoesophageal fistula and the dilated esophagus. CONCLUSION: The clinical adaptability of the Ni-Ti wire mesh-like stent is better than that of the stainless steel "Z" stent. For the patients with tracheoesophageal fistula, the first choice is covered-stent, while for the patients without tracheoesophageal fistula, uncovered-stent is better. The dilation of balloon is not necessary before the stent placement.

Aged↗
PubMed2003

[Establishment and application of in situ perfused pig ear model for percutaneous absorption].

AIM: To establish an in situ perfused pig ear model for percutaneous absorption. METHODS: The in situ perfused pig ear model for percutaneous absorption consisted of artificial gas, sample chamber, constant flow pump, constant temperature system, polytetrafluorethylene connective tube, porcine ear vein, porcine ear skin and special laminar flow apparatus. The perfused system viability was assessed by glucose utilization and lactate production. Ketoprofen isopropyl ester and methyl salicylate was used for validating this model. The concentrations of perfused sample were measured by HPLC. RESULTS: Glucose utilization and lactate production showed that this model was viable till 7 h. Ketoprofen isopropyl ester was completely metabolized to ketoprofen in situ in perfused pig ear model. The steady cumulative amount (Q) of ketoprofen from permeation and metabolism was linear with time (t), the equation of ketoprofen formation was Q = -0.024 + 0.120t, the rate of ketoprofen formation was 0.120 microgram.cm-2.h-1. Methyl salicylate was partially metabolized to salicylic acid. The steady cumulative amount (Q) of methyl salicylate from permeation was linear with time (t), the permeation equation of methyl salicylate was Q = -3.809 + 6.129t, the permeation rate of metyl salicylate was 6.129 micrograms.cm-2.h-1. The steady cumulative amount (Q) of salicylic acid from metabolism was also linear with time (t), the formation equation of salicylic acid was Q = -1.785 + 0.879t, the formation rate of salicylic acid was 0.879 microgram.cm-2.h-1. CONCLUSION: The in situ pig ear vein perfused model is a novel easy-handing and cost-efficient technique for percutaneous absorption and skin metabolism.

Administration, Cutaneous↗