Biomedical subjects

Lin Zhang

Publications and source records attributed to Lin Zhang.

At least 127 records · Page 7Linked to original sources

PubMed2005

Matrine improves 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice.

Matrine is an alkaloid found in kinds of Sophora plants mainly including Sophora flavescens, Sophora alopecuroides and Sophora subprotrata. The aim of the present study was to evaluate therapeutic effects of matrine on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Two hours following colonic instillation of TNBS, matrine with several doses was given by gastric gavage once daily for 7 days. Comparing with the 0.9% NaCl-treated mice with TNBS-induced colitis, matrine (10 and 20 mg kg(-1))-treated mice with TNBS-induced colitis were shown improvements of weight loss, macroscopic score, histological score, and myeloperoxidase (MPO) activity. Moreover, treatments with matrine (10 and 20 mg kg(-1)) decreased the up-regulated mRNA and protein levels of tumour necrosis factor-alpha (TNF-alpha) caused by TNBS. Our findings suggest that matrine improves TNBS-induced colitis in mice and the therapeutic mechanism might be related to the reduction of up-regulated colonic TNF-alpha production caused by TNBS.

Alkaloids↗

PubMed2005

Phosphatidylinositol-3-kinase signaling mediates vascular smooth muscle cell expression of periostin in vivo and in vitro.

OBJECTIVE: Periostin is dramatically upregulated in rat carotid arteries after balloon injury. The objective of the present study was to understand mechanisms underlying periostin upregulation in balloon-injured rat carotid arteries and in cultured vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: Periostin protein was strongly expressed at 3 days (in the medial SMCs) and 7 days (in the neointima) after injury. It was also abundantly expressed in the neointima in the late phase (at 14 and 28 days) after injury. Periostin upregulation was mediated through PI-3-kinase-dependent signaling pathway. In vivo, wortmannin, a PI-3-kinase inhibitor, inhibited balloon injury-induced Akt phosphorylation and periostin mRNA expression. In vitro, periostin mRNA expression in cultured VSMCs was stimulated by growth factors (transforming growth factor-beta1 (TGF-beta1), fibroblast growth factors (FGFs), PDGF-BB, and angiotensin II). This stimulatory effect was inhibited by the PI-3-kinase inhibitor LY294002. Further, periostin protein was mostly located in the cytoplasma of VSMCs in culture and abundantly secreted into the culture medium (CM) after stimulation with FGF-2, which significantly promoted VSMC migration in vitro. Immunodepletion of periostin from the VSMC-CM or blockade of periostin function with an anti-periostin antibody significantly reduced VSMC migration. CONCLUSIONS: Upregulation of periostin expression in rat carotid arteries following balloon injury and in cultured VSMCs after stimulation by growth factors is mediated through PI-3-kinase-dependent signaling pathway. Periostin protein secreted by VSMCs plays a significant role in regulating VSMC migration in vitro.

Androstadienes↗

PubMed2005

Strain and temperature sensitivity of a single-mode polymer optical fiber.

We have measured the optical phase sensitivity of fiber based on poly(methyl methacrylate) under near-single-mode conditions at 632.8 nm wavelength. The elongation sensitivity is 131 +/- 3 x 10(5) rad m(-1) and the temperature sensitivity is -212 +/- 26 rad m(-1) K(-1). These values are somewhat larger than those for silica fiber and are consistent with the values expected on the basis of the bulk polymer properties.

Journal Article↗

PubMed2005

Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10).

OBJECTIVES: Atherosclerosis is the leading cause of death in the United States, and human cytomegalovirus (HCMV) infection may play a role in the development of this disease. Diminished expression and/or activity of endothelial nitric oxide synthase (eNOS) are an early event in atherogenesis. In the current study, we investigated the effects of HCMV infection on eNOS activation in human aortic endothelial cells (HAECs). METHODS AND RESULTS: We found that HCMV inhibited eNOS phosphorylation/activation in HAECs. The signaling upstream of eNOS involving Akt and PDK1 were also suppressed by the HCMV infection. Moreover, HCMV infection increased the expression of PTEN (phosphatase and tensin homolog deleted on chromosome 10). Silencing PTEN expression with specific siRNA reversed the inhibitory effects on eNOS activation in HCMV-infected cells indicating the involvement of PTEN in mediating HCMV's inhibitory effects. Next we observed that the activation of p38 MAPK stress signaling pathway mediates HCMV's effects on PTEN up-regulation and eNOS inactivation. CONCLUSIONS: In summary, our findings suggest that inhibition of eNOS leading to endothelial dysfunction may be a basis of the pro-atherogenic effects of HCMV. Importantly, upregulation of PTEN and activation of stress signal p38 MAPK are involved in HCMV's inhibitory effects on eNOS activation.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2005

Transverse load and orientation measurement with multicore fiber Bragg gratings.

We demonstrate the sensitivity of Bragg gratings in a multicore fiber to transverse load. The Bragg peaks are split because of stress-induced birefringence, the magnitude of which depends upon the load and grating position relative to the load axis. Experiments show that a set of gratings in a four-core fiber can measure a load axis angle to +/- 5 degrees and a load magnitude to +/- 15 N m(-1) up to 2500 N m(-1). We consider alternative designs of multicore fiber for optimal load sensing and compare experimental and modeled data.

Journal Article↗

PubMed2005

Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death.

Ventricular tachycardia (VT) is the leading cause of sudden death, and the cardiac ryanodine receptor (RyR2) is emerging as an important focus in its pathogenesis. RyR2 mutations have been linked to VT and sudden death, but their precise impacts on channel function remain largely undefined and controversial. We have previously shown that several disease-linked RyR2 mutations in the C-terminal region enhance the sensitivity of the channel to activation by luminal Ca2+. Cells expressing these RyR2 mutants display an increased propensity for spontaneous Ca2+ release under conditions of store Ca2+ overload, a process we referred to as store overload-induced Ca2+ release (SOICR). To determine whether common defects exist in disease-linked RyR2 mutations, we characterized 6 more RyR2 mutations from different regions of the channel. Stable inducible HEK293 cell lines expressing Q4201R and I4867M from the C-terminal region, S2246L and R2474S from the central region, and R176Q(T2504M) and L433P from the N-terminal region were generated. All of these cell lines display an enhanced propensity for SOICR. HL-1 cardiac cells transfected with disease-linked RyR2 mutations also exhibit increased SOICR activity. Single channel analyses reveal that disease-linked RyR2 mutations primarily increase the channel sensitivity to luminal, but not to cytosolic, Ca2+ activation. Moreover, the Ca2+ dependence of [3H]ryanodine binding to RyR2 wild type and mutants is similar. In contrast to previous reports, we found no evidence that disease-linked RyR2 mutations alter the FKBP12.6-RyR2 interaction. Our data indicate that enhanced SOICR activity and luminal Ca2+ activation represent common defects of RyR2 mutations associated with VT and sudden death. A mechanistic model for CPVT/ARVD2 is proposed.

Animals↗

PubMed2005

Isolation of a triazophos-degrading strain Klebsiella sp. E6 effectively utilizing triazophos as sole nitrogen source.

A triazophos-degrading strain, Klebsiella sp. E6, was isolated by enrichment technology from soil that had been exposed long-term to triazophos. The strain grew well at pH 7.0-8.0 with a broad temperature profile ranging from 32 to 37 degrees C. It could keep good growth on methanol as carbon source and TAP as additional carbon source or nitrogen source. The experiment on the degradation activities of strain E6 showed that it utilized TAP more effectively when TAP was supplied as the sole nitrogen source, as opposed to additional carbon source. The intermediates of triazophos metabolism indicated that degradation occurred through a hydrolysis mechanism, one of the products of which, 1-phenyl-3-hydroxy-1,2,4-triazole, was also mineralized by strain E6.

Biodegradation, Environmental↗

PubMed2005

Optimizing a dansylhydrazine (DNSH) based method for measuring airborne acrolein and other unsaturated carbonyls.

The Passive Aldehydes and Ketones Sampler (PAKS) method has been developed to measure airborne carbonyls (aldehydes and ketones) by derivatizing the carbonyls with dansylhydrazine (DNSH) on a solid sorbent. The method collection efficiencies are approximately 100% for most saturated carbonyls, but are significantly lower for unsaturated carbonyls. In this study, we examined the mechanisms of DNSH reactions with unsaturated carbonyls, focusing on acrolein. With a better understanding of these mechanisms, we modified the sampling substrate conditions and HPLC analysis conditions of the original PAKS method, resulting in substantially improved collection efficiencies for acrolein and crotonaldehyde. Evaluated under a variety of conditions (temperature, humidity, presence of ozone), the modified PAKS method had a collection efficiency of 99%+/- 5% for acrolein (N= 36) and 96%+/- 20% for crotonaldehyde (N= 6). The acrolein-DNSH derivative was stable within 9.6% of the initial amount, after 14 days of storage at 4 degrees C, on the collection medium; and stable within 2.8% of the initial amount, after 16 days of storage at room temperature, in extract.

Acrolein↗

PubMed2005

Formation of uniform CuO nanorods by spontaneous aggregation: Selective synthesis of CuO, Cu2O, and Cu nanoparticles by a solid-liquid phase arc discharge process.

Uniform and monodisperse CuO nanorods have been synthesized by directional aggregation and crystallization of tiny CuO nanoparticles generated from a solid-liquid arc discharge process under ambient conditions in the absence of any surfactants. Uniform CuO nanorods with sharp ends are formed from tiny nanoparticles via a process that involves the rapid oxidation of Cu nanoclusters, the spontaneous aggregation of CuO nanoparticles, and the Ostawald ripening process. The spontaneous aggregation and oriented attachment of tiny CuO nanoparticles contributed obviously to the formation of these kinds of nanostructures. By choice of suitable reducing agent to prevent the oxidation of Cu nanoclusters, Cu and Cu2O nanoparticles can be selectively synthesized.

Journal Article↗

PubMed2005

Posterior cingulate gyrus metabolic changes in chronic schizophrenia with generalized cognitive deficits.

N-Methyl-d-aspartate (NMDA) receptor antagonists are known to induce schizophrenia-like psychotic symptoms and cognitive deficits in humans, and have been shown to cause neuronal damage in the posterior cingulate gyrus (PCG) of rodents. Patients with chronic schizophrenia exhibit generalized cognitive deficits, but it remains unclear whether or not the PCG is related to their cognitive dysfunction. To determine what biochemical changes may occur in the PCG of patients with chronic schizophrenia, and to ascertain whether or not such abnormalities may be related to the incidence of cognitive deficits, we obtained cognitive scores and proton magnetic resonance spectra (MRS) from the PCG and the left and right medial temporal lobes (MTL) of 19 patients with schizophrenia and 18 age- and sex-matched normal healthy controls. Compared to the normal controls, the patients with chronic schizophrenia showed significantly worse cognitive performance on verbal and visual memory tests, verbal fluency tests, and the Trail Making Test. The ratio of N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the PCG of the patients was significantly lower than that of the controls. Moreover, the NAA/Cr in the PCG of the healthy controls exhibited age-related decline, whereas in the patients with schizophrenia, the corresponding values were consistently low, regardless of age. These findings are thus in accord with current speculation about neuronal dysfunction in the PCG based on the NMDA hypofunction hypothesis regarding the pathophysiology of chronic schizophrenia.

Adult↗

PubMed2005

A homochiral porous metal-organic framework for highly enantioselective heterogeneous asymmetric catalysis.

A homochiral porous noninterpenetrating metal-organic framework (MOF), 1, was constructed by linking infinite 1D [Cd(mu-Cl)2]n zigzag chains with axially chiral bipyridine bridging ligands containing orthogonal secondary functional groups. The secondary chiral dihydroxy groups accessible via the large open channels in 1 were utilized to generate a heterogeneous asymmetric catalyst for the addition of diethyzinc to aromatic aldehydes to afford chiral secondary alcohols at up to 93% enantiomeric excess (ee). Control experiments with dendritic aromatic aldehydes of different sizes indicate that the heterogeneous asymmetric catalyst derived from 1 is both highly active and enantioselective as a result of the creation of readily accessible, uniform active catalyst sites inside the porous MOF.

Aldehydes↗

PubMed2005

[Effects of Her-2/neu siRNA-mediated gene silencing on cell cycle and apoptosis of lung adenocarcinoma cells].

OBJECTIVE: To investigate the effect of synthesized Her-2/neu specific siRNA on the cell cycle and apoptosis of Her-2/neu upregulating human lung adenocarcinoma cells. METHODS: Human lung cancer cells of the line calu-3 were cultured and divided into 4 groups: untreated control group, blank vector group transfected with blank vector, non-specific siRNA group transfected with unrelated siRNA, and Her2/neu siRNA group transfected with Her2/neu siRNA. RT-PCR was used to examine the Her-2/neu and cyclin D(1) mRNA expression. Flow cytometry was used to examine the Her-2/neu protein expression and cell cycle. The apoptosis rate was analyzed by using annexin V-FITC kit. The vascular endothelial growth factor (VEGF) level in the culture supernatant was detected by ELISA. RESULTS: Twenty-four hours after transfection, the expressions of Her-2/neu mRNA and cyclin D1 mRNA in the Her2/neu siRNA group decreased remarkably, both significantly lower than those in the other 3 groups. Forty-eight hours after transfection, the expression rate of Her-2/neu protein was 25.0% +/- 1.6% in the calu-3 cells transfected with Her-2/neu siRNA, significantly lower than in the control group, blank vector group, and non-specific siRNA group (98.2% +/- 2.2%, 95.7% +/- 2.0%, and 94.8% +/- 1.6% respectively, all P < 0.01); the proportion of the cells in G(0)/G(1) stage increased and those in the S stage decreased in the celu-3 cells transfected with Her-2/neu siRNA, and the proportions of the cells in G(0)/G(1) stage and Stage did not significantly change (F = 6.1, P < 0.01); the apoptotic rate of the Her2/neu siRNA group was 25.1% +/- 1.2%, significantly higher than those of the other 3 groups (4.8% +/- 0.5%, 8.6% +/- 0.9%, and 10.3% +/- 0.3% respectively, all P < 0.01); the caspase-3 activity ratio of the Her2/neu siRNA group was 134.6% +/- 4.5%, significantly higher than those in the blank vector group and non-specific siRNA group (105.0% +/- 2.5% and 112.0% +/- 2.8% respectively, both P < 0.01), and the VEGF level in the supernatant of the Her2/neu siRNA group was 176 pg/ml +/- 6 pg/ml, significantly lower than those of the control group, blank vector group, and non-specific siRNA group (476 pg/ml +/- 13 pg/ml, 426 pg/ml +/- 9 pg/ml, and 406 pg/ml +/- 9 pg/ml respectively, all P < 0.01). CONCLUSION: Chemically synthesized Specific Her-2/neu targeting siRNA effectively inhibits Her-2/neu expression and leads to the decline of cyclin D(1) and VEGF levels and activation of caspase-3 pathway thus arresting the cell cycle at G(0)/G(1) stage and enhancing cell apoptosis.

Adenocarcinoma↗

PubMed2005

The transcriptional targets of p53 in apoptosis control.

Induction of apoptosis is an essential function of p53 as a tumor suppressor. p53 can activate its downstream targets in a sequence specific manner to induce apoptosis. Most tumor derived p53 mutants are deficient in transcription activation as well as apoptosis induction. p53 can activate genes in the extrinsic and intrinsic pathways through transcription-dependent mechanisms or induce apoptosis through transcription-independent mechanisms. Several proapoptotic Bcl-2 family proteins, such as PUMA and Noxa, are shown to be critical mediators of p53-dependent apoptosis. The selective activation of the apoptotic targets of p53 is modulated by transcription coactivators. The induction of apoptotic genes alone sometimes is not sufficient to induce apoptosis, as the cell cycle arrest mediated by the cell cycle inhibitors dominates apoptosis. Preventing the induction of p21 under these conditions can drive the cells towards apoptosis. Understanding how p53 controls apoptosis through its targets may lead to discoveries of novel therapeutics to combat cancer and other diseases.

Animals↗

PubMed2005

Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with Cisplatin in solid tumors.

PURPOSE: CXC chemokine ligand 10 (CXCL10) is a potent inhibitor of angiogenesis. We wonder whether the combination of CXCL10 with cisplatin would improve the therapeutic antitumor efficacy. EXPERIMENT DESIGN: We evaluated the antitumor activity of the combination therapy in the immunocompetent C57BL/6 and BALB/c mice bearing LL/2 Lewis lung cancer and CT26 colon adenocarcinoma, respectively. Mice were treated with either CXCL10 s.c. at 25 mug per kg per day once daily for 30 days, cisplatin cycled twice (5 mg/kg i.p. on days 14 and 21 after the initiation of CXCL10), or both agents together. Tumor volume and survival time were observed. Antiangiogenesis of CXCL10 in vivo were determined by alginate capsule models and CD31 immunohistochemistry. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues. RESULTS: CXCL10 + cisplatin reduced tumor growth in LL/2 and CT26 tumor model, respectively, more effectively, although cisplatin or CXCL10 individually resulted in suppression of tumor growth and improved survival time of tumor-bearing mice. CXCL10 successfully inhibited angiogenesis as assessed by alginate model and CD31 (P < 0.05). Histologic analysis of tumors exhibited that CXCL10 in combination with cisplatin led to the increased rate of apoptosis, tumor necrosis, and elevated lymphocyte infiltration. CONCLUSIONS: Our data suggest that the combination of CXCL10, a well-tolerated angiogenesis inhibitor, with cisplatin can enhance the antitumor activity. The present findings may be of importance to the further exploration of the potential application of this combined approach in the treatment of lung and colon carcinoma.

Animals↗

PubMed2005

High extinction ratio in-fiber polarizers based on 45 degree tilted fiber Bragg gratings.

We report a near-ideal in-fiber polarizer implemented by use of 45 degrees tilted fiber Bragg grating structures that are UV inscribed in hydrogenated Ge-doped fiber. We demonstrate a polarization-extinction ratio of 33 dB over a 100-nm operation range near 1550 nm. We further show an achievement of 99.5% degree of polarization for unpolarized light with these gratings. We also theoretically investigate tilted grating structures based on the Green's function calculation, therein revealing the unique polarization characteristics, which are in excellent agreement with experimental data.

Journal Article↗

PubMed2005

HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer.

Cooperation between oncolytic herpes simplex virus (HSV) and host effector immune mechanisms has been previously described. In the present study, we investigated the mechanism underlying such cooperation in a murine syngeneic model of ovarian carcinoma. Therapeutic administration of HSV-1716, a replication-restricted mutant, resulted in significant reduction of tumor growth and a significant survival advantage. Intratumoral injection of HSV-1716 induced expression of IFN-gamma, MIG, and IP-10 in the tumor. This was accompanied by a significant increase in the number of tumor-associated NK and CD8+ T cells expressing CXCR3 and CD25. Ascites from HSV-1716-treated animals efficiently induced in vitro migration of NK and CD8+ T cells, which was dependent on the presence of MIG and IP-10. Murine monocytes and dendritic cells (DCs) were responsible for the production of MIG and IP-10 upon HSV-1716 infection. In monocytes, this was partially abrogated by neutralizing antibodies against IFN-alpha and -beta, thus indicating a role for type-1 IFNs in the reported effect. Human ovarian carcinomas showed high numbers of monocytes and DCs. Upon HSV-1716 infection, human monocyte-derived DCs produced large amounts of IFN-gamma and upregulated MIG and IP-10 expression. These results indicate that HSV-1716 induces an inflammatory response that may facilitate antitumor immune response upon oncolytic therapy.

Animals↗

PubMed2005

Comparison of hepatic coagulant, fibrinolytic, and anticoagulant functions between Banna Minipig Inbred line and humans.

BACKGROUND: As an ideal candidate for xenotransplantation, the compatibility of physiological porcine organs with those of humans is an essential premise. In this study, we analyzed hepatic coagulant, fibrinolytic, and anticoagulant functions between Banna Minipig Inbreds (BMIs) and humans to evaluate such hepatic compatibility. METHODS: BMI factors II, V, VII, X, and XII were added to the corresponding factor-deficient human plasma to determine prothrombin times (PT) and activated partial thromboplastin times (APTT). Human tissue plasminogen activator (t-PA) was added to both BMI and human plasma to determine plasmin activity. The antithrombin-III (AT-III) activity of plasma was analyzed with the STA-Stago autoanalyzer using an AT-III assay kit. RESULTS: Both PT and APTT were reduced but within normal parameters when BMI factors II, V, VII, X, and XII were added to the corresponding factor-deficient human plasma. The activities of BMI coagulation factors II, V, VII, X, and XII were 3.2, 3.7, 4.7, 2.9, and 4.5 times those of humans, respectively. The activity of plasmin was significantly higher in BMI plasma than in humans when human t-PA was added to both. The normal range of human AT-III activity was 90-108% while BMI AT-III was 124.50 +/- 2.38%. CONCLUSIONS: The activities of coagulation factors and AT-III were higher in BMIs than in humans. BMI coagulation factors XII, VII, and X trigger human intrinsic, extrinsic, and common pathways, respectively, which functioned normally. In addition, BMI plasminogen could be activated by human t-PA.

Adult↗

PubMed2005

Potent activity of a novel dimeric heat shock protein 90 inhibitor against head and neck squamous cell carcinoma in vitro and in vivo.

Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical testing. However, 17-AAG is difficult to formulate and displays weak activity against some tumors. A novel dimeric ansamycin, EC5, was evaluated for antitumor activity in eight head and neck squamous cell carcinoma (HNSCC) cell lines. Both 17-AAG and EC5 inhibited tumor cell proliferation effectively, but EC5 was more potent, with IC(50) below 200 nmol/L in most cell lines tested, including several lines that were resistant to 17-AAG. The inability of 17-AAG to kill JHU12 cells was linked to a defect in retinoblastoma signaling and could be rescued by ectopic expression of p16(INK4a). EC5 induced G(1) growth arrest of tumor cells and apoptosis, with the degradation of client proteins including epidermal growth factor receptor, c-Raf-1, Akt, and Cdk4 and inhibition of Akt phosphorylation. In vivo, EC5 dramatically reduced the growth rate of established HNSCC xenografts in nude mice and decreased expression of epidermal growth factor receptor and Akt within the xenografts. These results suggest that this novel ansamycin-based Hsp90 inhibitor affects multiple pathways involved in tumor development and progression and may represent a new strategy for the treatment of HNSCC patients.

Animals↗