Biomedical subjects

Hong Zhu

Publications and source records attributed to Hong Zhu.

At least 55 records · Page 3Linked to original sources

PubMed2005

Excitatory amino acid receptors are involved in morphine-induced synchronous oscillatory discharges in the locus coeruleus of rats.

Our previous studies demonstrated that morphine not only decreases the firing rate of locus coeruleus neurons, but that it induces synchronous oscillatory discharges in the locus coeruleus. In the present study, we examined the role of excitatory amino acid input in the mechanisms of the morphine-induced synchronous oscillation in the locus coeruleus. Using a multiple-electrode recording technique, locus coeruleus neuronal activities were recorded under halothane anesthesia in adult Sprague-Dawley rats. Among 175 locus coeruleus neurons recorded after intracerebroventricular (i.c.v.) injection of morphine (26 nmol), 88 of them exhibited both decreased firing rates and synchronous oscillatory discharges. The morphine-induced oscillation and synchrony were reversed by i.c.v. injection of the non-selective excitatory amino acid receptor antagonist kynurenic acid, the selective NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5), or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not saline vehicle. These results suggest that excitatory amino acid input contributes to the morphine-induced synchronous oscillatory activity in the locus coeruleus. The results also provide us a pharmacology tool to study the influence of blockade of the locus coeruleus synchrony on neurotransmitter release and synaptic plasticity in the locus coeruleus target areas.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2005

Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress.

Resveratrol (3,4',5-trihydroxystilbene), a polyphenolic compound found in mulberries, grapes and red wine has been demonstrated to be capable of protecting against oxidative cardiovascular pathophysiology. However, the underlying cellular and biochemical mechanisms remain to be elucidated. This study was undertaken to determine if resveratrol could upregulate endogenous antioxidants and phase 2 enzymes in cultured aortic smooth muscle cells (ASMCs), and if such increased cellular defenses could provide protection against oxidative and electrophilic vascular cell injury. Incubation of rat ASMCs with resveratrol at low micromolar concentrations resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. These cytoprotective factors include superoxide dismutase, catalase, glutathione, glutathione reductase, glutathione peroxidase, glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NOQ1). Notably, induction of catalase, GST, and NOQ1 was most remarkable among the above resveratrol-inducible antioxidants and phase 2 enzymes. Moreover, resveratrol treatment also significantly increased the mRNA expression of catalase, GSTA1, and NQO1 in a time-dependent manner. Pretreatment of ASMCs with resveratrol afforded a remarkable protection against xanthine oxidase (XO)/xanthine- or 4-hydroxy-2-nonenal-induced cytotoxicity, as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Resveratrol pretreatment also led to a marked reduction in intracellular accumulation of reactive oxygen species in ASMCs after incubation with XO/xanthine. Taken together, this study demonstrates that a scope of key endogenous antioxidants and phase 2 enzymes in cultured ASMCs can be upregulated by resveratrol at low micromolar concentrations, and that such chemically-elevated cellular defenses rendered cells increased resistance to oxidative and electrophilic stress. The results of this study thus suggested a new mechanism, which might contribute to the cardiovascular protective effects of resveratrol.

Aldehydes↗

PubMed2005

Isolation and characterization of a cDNA encoding two novel heat-shock factor OsHSF6 and OsHSF12 in Oryza sativa L.

As a crucial transcription factor family, heat-shock factors were mainly analyzed and characterized in tomato and Arabidopsis. In this study, we isolated two putative heatshock factors OsHSF6 and OsHSF12 that interact specifically with heat-shock element (HSE) from Oryza sativa L by yeast one-hybrid method. The full-length cDNA of OsHSF6 and OsHSF12 have 1074bp and 920bp open reading frame (ORF), respectively. Analysis of the deduced amino acid sequences revealed that OsHSF6 was a class A heat shock factor (HSF) with all the conserved sequence elements characteristic of heat stress transcription factor, while OsHSF12 was a class B HSF with C-terminal domain (CTD) lacking of AHA motif. Bioinformatic analysis showed that the sequences and structures of two HSFs' DNA binding domain (DBD) had a high similarity with LpHSF24. The results of RT-PCR indicated OsHSF6 gene was expressed immediately after rice plants exposure to heat stress, and the transcription of OsHSF6 gene accumulated primarily in immature seeds, roots and leaves. However, we did not find the transcription of OsHSF12 gene in different organs and growth periods. Our results implied that OsHSF6 might be function as a HSF regulating early expression of stress genes in response to heat shock, and OsHSF12 might be act as a synergistic factor to regulate the expression of down-stream genes.

Amino Acid Sequence↗

PubMed2005

Study of hydrolysis and acidification process to minimize excess biomass production.

In this paper, a new wastewater treatment process has been presented to minimize excess biomass production in which both excess sludge digestion and wastewater treatment are conducted simultaneously in the system. The process is modification of conventional activated sludge process with insertion of two facultative basins in the sludge return line. The excess biomass in the aeration tank is recirculated to the first facultative tank. It was observed that: (1) The amount of excess biomass is reduced to nearly aero when 5.95 g/day excess sludge is recirculated from the aeration tank to the first facultative tank at COD(Cr) loading of 2.31 kg/m(3)day. A biomass experiment of 1000 mg/L was maintained at 2.31 kg-COD(Cr)/m(3)day without drawing excess sludge for 6 months of experiment period. Inert organic substances did not seem to accumulate. The effluent quality has been well below the discharge limit. (2) On the basis of infrared spectroscopy proved that dye molecule in wastewater were firstly absorbed on the sludge, and then the bond energy of was gradually weakened and decomposed and eliminated lastly.

Biomass↗

PubMed2005

Selective uptake and efflux of cholesteryl linoleate in LDL by macrophages expressing 12/15-lipoxygenase.

Oxidation of low density lipoprotein (LDL) is a critical step for atherogenesis, and the role of the 12/15-lipoxygenase (12/15-LOX) as well as LDL receptor-related protein (LRP) expressed in macrophages in this process has been suggested. The oxygenation of cholesteryl linoleate in LDL by mouse macrophage-like J774A.1 cells overexpressing 12/15-LOX was inhibited by an anti-LRP antibody but not by an anti-LDL receptor antibody. When the cells were incubated with LDL double-labeled by [3H]cholesteryl linoleate and [125I]apoB, association with the cells of [3H]cholesteryl linoleate expressed as LDL protein equivalent exceeded that of [125I]apoB, indicating selective uptake of [3H]cholesteryl linoleate from LDL to these cells. An anti-LRP antibody inhibited the selective uptake of [3H]cholesteryl ester by 62% and 81% with the 12/15-LOX-expressing cells and macrophages, respectively. Furthermore, addition of LDL to the culture medium of the [3H]cholesteryl linoleate-labeled 12/15-LOX-expressing cells increased the release of [3H]cholesteryl linoleate to the medium in LDL concentration- and time-dependent manners. The transport of [3H]cholesteryl linoleate from the cells to LDL was also inhibited by an anti-LRP antibody by 75%. These results strongly suggest that LRP contributes to the LDL oxidation by 12/15-LOX in macrophages by selective uptake and efflux of cholesteryl ester in the LDL particle.

Animals↗

PubMed2005

Reactive oxygen species elicit apoptosis by concurrently disrupting topoisomerase II and DNA-dependent protein kinase.

Reactive oxygen species (ROS) are produced by all aerobic cells and have been implicated in the regulation of diverse cellular functions, including intracellular signaling, transcription activation, proliferation, and apoptosis. Salvicine, a novel diterpenoid quinone compound, demonstrates a broad spectrum of antitumor activities. Although salvicine is known to trap the DNA-topoisomerase II (Topo II) complex and induce DNA double-strand breaks (DSBs), its precise antitumor mechanisms remain to be clarified. In this study, we investigated whether salvicine altered the levels of ROS in breast cancer MCF-7 cells and whether these ROS contributed to the observed antitumoral activity. Our data revealed that salvicine stimulated intracellular ROS production and subsequently elicited notable DSBs. The addition of N-acetyl cysteine (NAC), an antioxidant, effectively attenuated the salvicine-induced ROS enhancement and subsequent DNA DSBs. Heat treatment reversed the accumulation of DNA DSBs, and the addition of NAC attenuated the Topo II-DNA cleavable complexes formation and the growth inhibition of salvicine-treated JN394top2-4 yeast cells, collectively indicating that Topo II is a target of the salvicine-induced ROS. On the other hand, when examining the impact of salvicine on DNA repair pathways, we unexpectedly observed that salvicine selectively down-regulated the catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) protein levels and repressed DNA-PK kinase activity; both of these effects were attenuated by NAC pretreatment of MCF-7 cells. Finally and most importantly, NAC attenuated salvicine-induced apoptosis and cytotoxicity in MCF-7 cells. These results indicate that apart from its direct actions, salvicine generates ROS that modulate DNA damage and repair, contributing to the comprehensive biological consequences of salvicine treatment, such as DNA DSBs, apoptosis, and cytotoxicity in tumor cells. The finding of salvicine-induced ROS provides new evidence for the molecular mechanisms of this compound. Moreover, the effects of salvicine-induced ROS on Topo II and DNA-PK give new insights into the diverse biological activities of ROS.

Acetylcysteine↗

PubMed2005

Expression and significance of new inhibitor of apoptosis protein survivin in hepatocellular carcinoma.

AIM: To investigate expression and significance of inhibitor of apoptosis protein survivin in hepatocellular carcinoma (HCC). METHODS: The expression of survivin and vascular endothelial growth factor (VEGF) was investigated in 38 cases of HCC tissues and 38 liver cirrhosis tissues by immunohistochemistry and Western blot. The relationship between the expression of survivin and clinicopathological factors of HCC was analyzed. RESULTS: Survivin protein was detected in 23 (60.5%) of 38 HCCs and 3 (7.9%) of 38 liver cirrhosis tissues. In 23 cases of HCC which expressed survivin, the expression of VEGF was positive in 18 cases and slight positive or negative in 5 cases. While in 15 cases of HCC which did not express survivin, 12 cases did not express or slightly expressed, and 3 cases expressed VEGF. In liver cirrhosis tissues, the expression of VEGF was as follows: 24 cases were negative, 10 cases were weak positive and 4 cases were strong positive. The expression of survivin was coincident with the expression of VEGF in HCC (P<0.01). The expression of survivin in HCC had no relationship with the patients' age, gender, tumor size and differentiation level of HCC, while it was related to the metastasis of HCC. The protein quantitative analysis by Western blot also showed that overexpression of survivin in HCC was closely correlated to the expression of VEGF (P<0.01). Furthermore, stronger expression of survivin and VEGF was also found in patients with metastasis rather than in those with no metastasis (P<0.01). CONCLUSION: Survivin plays a pivotal role in the metastasis of HCC, and it has some correlation with tumorigenesis. The expression of survivin in the primary lesion is very useful as an indicator for metastasis and prognosis of HCC. It could become a new target of gene therapy of HCC.

Adult↗

PubMed2005

Differential roles of 3H-1,2-dithiole-3-thione-induced glutathione, glutathione S-transferase and aldose reductase in protecting against 4-hydroxy-2-nonenal toxicity in cultured cardiomyocytes.

4-hydroxy-2-nonenal (HNE) plays an important role in the pathogenesis of cardiac disorders. While conjugation with glutathione (GSH) catalyzed by GSH S-transferase (GST) has been suggested to be a major detoxification mechanism for HNE in target cells, whether chemically upregulated cellular GSH and GST afford protection against HNE toxicity in cardiac cells has not been investigated. In addition, the differential roles of chemically induced GSH and GST as well as other cellular factors in detoxifying HNE in cardiomyocytes are unclear. In this study, we have characterized the induction of GSH and GST by 3H-1,2-dithiole-3-thione (D3T) and the protective effects of the D3T-elevated cellular defenses on HNE-mediated toxicity in rat H9C2 cardiomyocytes. Treatment of cardiomyocytes with D3T resulted in a significant induction of both GSH and GST as well as the mRNA expression of gamma-glutamylcysteine ligase catalytic subunit and GSTA. Both GSH and GST remained elevated for at least 72 h after removal of D3T from the culture media. Treatment of cells with HNE led to a significant decrease in cell viability and an increased formation of HNE-protein adducts. Pretreatment of cells with D3T dramatically protected against HNE-mediated cytotoxicity and protein-adduct formation. HNE treatment caused a significant decrease in cellular GSH level, which preceded the loss of cell viability. Either depletion of cellular GSH by buthionine sulfoximine (BSO) or inhibition of GST by sulfasalazine markedly sensitized the cells to HNE toxicity. Co-treatment of cardiomyocytes with BSO was found to completely block the D3T-mediated GSH elevation, which however failed to reverse the cytoprotective effects of D3T, suggesting that other cellular factor(s) might be involved in D3T cytotprotection. In this regard, D3T was shown to induce cellular aldose reductase (AR). Surprisingly, inhibition of AR by sorbinil failed to potentiate HNE toxicity in cardiomyocytes. In contrast, sorbinil dramatically augmented HNE cytotoxicity in cells with GSH depletion induced by BSO. Similarly, in BSO-treated cells, D3T cytoprotection was also largely reversed by sorbinil, indicating that AR played a significant role in detoxifying HNE only under the condition of GSH depletion in cardiomyocytes. Taken together, this study demonstrates that D3T can induce GSH, GST, and AR in cardiomyocytes, and that the above cellular factors appear to play differential roles in detoxification of HNE in cardiomyocytes.

Aldehyde Reductase↗

PubMed2005

Nude mice multi-drug resistance model of orthotopic transplantation of liver neoplasm and Tc-99m MIBI SPECT on p-glycoprotein.

AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy. METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected subdermally to form the tumor-supplying mice. The orthotopic drug-resistant tumors were formed by implanting the tumor bits under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and visual inspection were used to examine tumor progression. RT-PCR and immunohistochemistry were used to detect expression of mdr1 mRNA and its encoded protein p-glycoprotein (p-gp). Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 20 min after injection, and the liver/heart ratios were calculated. RESULTS: Post-implantation mortality was 0% (0/25), tumor implantation success was 90% (22/25), and the rate of implanting successfully for the second time was 100% (3/3). Tumor induction using Pharmorubicin was 80% (16/20). The mdr1 mRNA expression of the induced group was 23 times higher than that of the control group, and p-gp protein expression was 13-fold higher compared to the control group. The liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased significantly in the induced group as compared to the control group. CONCLUSION: We have established an in vivo model of mdr1 in nude mice by orthotopic transplantation of liver neoplasm coupled to chemotherapy. We propose that identification of drug resistance as characterized by decreased 99mTc-ppm radiography due to enhanced clearance by p-gp may be useful in detecting in vivo drug resistance, as well as a useful tool in designing more effective therapies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: protection against reactive oxygen and nitrogen species-induced cell injury.

Understanding the molecular pathway(s) of antioxidant gene regulation is of crucial importance for developing antioxidant-inducing agents for the intervention of oxidative cardiac disorders. Accordingly, this study was undertaken to determine the role of Nrf2 signaling in the basal expression as well as the chemical inducibility of endogenous antioxidants and phase 2 enzymes in cardiac fibroblasts. The basal expression of a scope of key cellular antioxidants and phase 2 enzymes was significantly lower in cardiac fibroblasts derived from Nrf2-/- mice than those from wild type control. These include catalase, reduced glutathione (GSH), glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). Incubation of Nrf2+/+ cardiac fibroblasts with 3H-1,2-dithiole-3-thione (D3T) led to a significant induction of superoxide dismutase (SOD), catalase, GSH, GR, glutathione peroxidase (GPx), GST, and NQO1. The inducibility of SOD, catalase, GSH, GR, GST, and NQO1, but not GPx by D3T was completely abolished in Nrf2-/- cells. The Nrf2-/- cardiac fibroblasts were much more sensitive to reactive oxygen and nitrogen species-mediated cytotoxicity. Upregulation of antioxidants and phase 2 enzymes by D3T in Nrf2+/+ cardiac fibroblasts resulted in a dramatically increased resistance to the above species-induced cytotoxicity. In contrast, D3T-treatment of the Nrf2-/- cells only provided a slight cytoprotection. Taken together, this study demonstrates for the first time that Nrf2 is critically involved in the regulation of the basal expression and chemical induction of a number of antioxidants and phase 2 enzymes in cardiac fibroblasts, and is an important factor in controlling cardiac cellular susceptibility to reactive oxygen and nitrogen species-induced cytotoxicity.

Animals↗

PubMed2005

[Epidemiological data of chronic obstructive pulmonary disease in Yanqing County in Beijing].

OBJECTIVE: To evaluate the epidemiological characteristic and risk factors of chronic obstructive pulmonary disease (COPD) in the rural area of Beijing. METHODS: The data of 1,624 people aged more than 40 in 5 villages in Yanqing County in Beijing were collected. The habitation condition, life and cooking habit, smoking history, personal history and family history were asked, and their physical examinations and lung function tests were conducted. RESULTS: The prevalence of COPD was 9.11% in this area, 15.05% in males and 3.76% in females. There were significant differences in sex, age, smoking history, family history, frequent cough before age 14 and body index between the COPD and non-COPD groups. The prevalence of corpulmonale was 1.66% in this area. CONCLUSION: The prevalence of COPD was high in this area and related with sex, age, smoking history, family history, frequent cough before age 14 and low body index. Other factors such as environment, working exposure need to be studied in the future. COPD is a major public health problem, which should claim more attention.

Adult↗

PubMed2005

Characterization of cell proliferation in the adult dentate under normal conditions and after kainate induced seizures using ribonucleotide reductase and BrdU.

Ribonucleotide reductase (RNR), an enzyme for DNA synthesis, was recently used as a marker of proliferating cells in the dentate gyrus and subventricular zone in normal adult mammalian brains. However, the duration of RNR expression in normal adult brain and the expression pattern of RNR in the adult dentate gyrus following brain injury have not been explored. In this study, we examined the duration of the RNR expression in newborn cells in the normal adult rat brain by analysis of RNR and BrdU double-labeled specimens at different time intervals after BrdU application. Secondly, we induced, in adult rats, seizures by kainic acid and investigated the changes in expression of RNR following seizures, and characterized the phenotype of RNR-positive cells using a variety of other markers. Our results revealed that RNR was detectable in proliferating cells from 2 h to at least 1 day. At 7 and 28 days after seizures, there was a fivefold increase in number of clusters of RNR-positive cells in the dentate gyrus, and a doubling of the number of BrdU-labeled cells in each cluster. Proliferating astrocytes and neuronal precursors were recognized in each RNR-positive cell cluster, and both types increased in number after seizures. Colocalization of RNR and activated caspase-3 was observed at 7 days, indicating that proliferating cells were susceptible to status epilepticus induced damage. RNR immunohistochemistry provides a useful approach in experiments investigating a change in cell proliferation, revealing the location, number, morphology and fate of newly formed cells after, e.g., brain injury.

Animals↗

PubMed2005

[Hypoxia-inducible factor-1 alpha dependent expression and significance of the related multidrug resistance genes induced by hypoxia in human hepatocarcinoma cell].

OBJECTIVE: To explore the mechanism of multidrug resistance of hepatocellular carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and multidrug resistance related genes. METHODS: Human hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung resistance protein (LRP) gene at the mRNA and the protein levels in the above two groups were respectively analyzed by real-time fluorescent quantitative PCR and Western-blot technique. RESULTS: In the hypoxia group, the expressions of mdr1, MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1 alpha. Also the increased expression of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid HIF-1 alpha/PCDNA3. CONCLUSIONS: Resistance of hepatocellular carcinoma to chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the upregulation of the expression of the related multidrug resistance genes induced by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of hepatocellular carcinoma.

Blotting, Western↗

PubMed2005

Pathology of guinea pigs experimentally infected with a novel reovirus and coronavirus isolated from SARS patients.

Guinea pigs were inoculated with a reovirus (ReoV) and coronavirus (SARS-CoV) isolated from SARS patients to determine their potential role in the etiology of SARS. Animals infected with ReoV died between day 22 and day 30 postinoculation (PI) while 70% of the animals inoculated with ReoV and SARS-CoV died between day 4 to day 7 PI. The titer of neutralizing antibodies against ReoV and SARS-CoV ranged from 80 to 160 when the animals were inoculated with the two viruses, respectively, while the titer of the antibodies was just below 10 in coinfections. The animal inoculated with ReoV developed diffuse alveolar damage similar to the exudative and leakage inflammation found in SARS patients, and was characterized by diffuse hemorrhage, fibroid exudation, hyaline membrane formation, and type II pneumocytes hyperplasia in alveolar interstitia. The pulmonary epithelial necrosis, excoriation, and early fibrosis of pulmonary tissue were only observed in ReoV-SARS-CoV groups and in SARS-CoV/ReoV groups. Other typical pathological changes included hemorrhagic necrosis in lymph nodes and spleen and hydropic degeneration in the liver. On the contrary, guinea pigs infected with SARS-CoV only developed interstitial pneumonitis. Our experiment demonstrate that ReoV might be one of the primary causes of SARS, since simultaneous coinfection can duplicate the typical pathological changes similar to that of SARS patients. This guinea pig model may provide a useful animal model for SARS.

Animals↗

PubMed2005

Experimental infection of macaques with the human reovirus BYD1 strain: an animal model for the study of the severe acute respiratory syndrome.

Experimental studies were performed to determine the role of a newly isolated reovirus (ReoV) from a severe acute respiratory syndrome (SARS) patient in the etiology of this newly described serious respiratory syndrome. Four cynomologus macaques were inoculated with this reovirus (BYD1) in an attempt to replicate the infection and pathology observed in SARS. The body temperature of the infected monkeys was monitored three times a day, and blood and fecal samples were periodically collected for specific immunology determinations. On days 7 and 33 after inoculation, necropsies for pathological accessment and pathogen isolation were performed. The four infected macaques developed a fever on days 3 and 4 after inoculation, and maintainted a febrile state for 4-6 days. The highest temperature in the animals recorded was 40.4 degrees C. After a recovery phase, the macaques developed a second febrile condition. Antibody titers against the reovirus injected by the intravenous route occurred in higher number than those in the nasal cavity. Four macaque monkeys demonstrated diffuse alveolar damage, characterized by hemorrhagic pneumonia, serosanguineous exudates, formation of hyaline membranes, and type II pneumocyte hyperplasia, which were similar to those that have been noted in SARS patients. Lymphocytes decreased in the cortex of the lymph node and in the white pulp of the spleen. ReoV was detected in pneumonic tissue by virus isolation and RT-PCR. The macaques infected with the newly isolated reovirus developed a fever, diffuse alveolar damage and pulmonary interstitial inflammation similar to that noted in SARS patients. This evidence demonstrates that ReoV might have a primary role in the etiology of SARS.

Animals↗

PubMed2005

Fabrication and characterization of piezoelectric micromachined ultrasonic transducers with thick composite PZT films.

Ferroelectric microelectromechanical systems (MEMS) has been a growing area of research in past decades, in which ferroelectric films are combined with silicon technology for a variety of applications, such as piezo-electric micromachined ultrasonic transducers (pMUTs), which represent a new approach to ultrasound detection and generation. For ultrasound-radiating applications, thicker PZT films are preferred because generative force and response speed of the diaphragm-type transducers increase with increasing film thickness. However, integration of 4- to 20-microm thick PZT films on silicon wafer, either the deposition or the patterning, is still a bottleneck in the micromachining process. This paper reports on a diaphragm-type pMUT. A composite coating technique based on chemical solution deposition and high-energy ball milled powder has been used to fabricate thick PZT films. Micromachining of the pMUTs using such thick films has been investigated. The fabricated pMUT with crack-free PZT films up to 7-microm thick was evaluated as an ultrasonic transmitter. The generated sound pressure level of up to 120 dB indicates that the fabricated pMUT has very good ultrasound-radiating performance and, therefore, can be used to compose pMUT arrays for generating ultrasound beam with high directivity in numerous applications. The pMUT arrays also have been demonstrated.

Computer-Aided Design↗

PubMed2005

Patterns of K-ras codon 12 and 13 mutations found in pancreatic adenocarcinoma of 30 Chinese patients by microdissection, PCR and direct sequencing.

BACKGROUND AND AIM: To our knowledge there are few reports on the K-ras mutation pattern of pancreatic adenocarcinoma from Chinese mainland patients. We examined surgically resected formalin-fixed, paraffin-embedded primary pancreatic adenocarcinoma tissue blocks for the presence of activating point mutations at codon 12 and 13 of the K-ras gene. METHODS: Mutations were detected through the use of microdissection, polymerase chain reaction (PCR) and direct sequencing. The results were confirmed by reverse sequencing. RESULTS: The combination of microdissection, PCR and direct sequencing techniques resulted in a rapid and sensitive detection of K-ras mutations at codon 12 and 13. Twenty-five (83%) of the 30 pancreatic adenocarcinomas examined harbored K-ras mutation. Among the 25 pancreatic adenocarcinomas, 24 showed K-ras mutation at codon 12 (11 with GGT-GTT, seven with GGT-GAT, four with GGT-CGT, and two with GGT-TGT), and only one showed a GGC-TGC mutation at codon 13. In this study most of K-ras mutations at codon 12 were at the second base (72%, 18/25) with a transition/transversion ratio of 1 : 1.57 (7/11). CONCLUSIONS: The mutation profiles of K-ras at codon 12 in our pancreatic adenocarcinoma samples were significantly different from those of European and Japanese samples.

Adenocarcinoma↗

PubMed2005

DNAzyme-mediated cleavage of survivin mRNA and inhibition of the growth of PANC-1 cells.

BACKGROUND AND AIM: Survivin has functions in both the regulation of cell division and the inhibition of apoptosis, and it is expressed in most human tumors but not in normal adult tissues. It is a potential target for cancer gene therapy. In the present study, we designed a DNAzyme targeting human survivin mRNA and tried to determine its effect on human pancreatic carcinoma cell line PANC-1. METHODS: We designed and synthesized a '10-23' antisurvivin mRNA DNAzyme, testified its cleavage activity by cell-free test, then delivered it into the PANC-1 cell line through liposome, and detected its effect on survivin mRNA expression by reverse transcription polymerase chain reaction, Western blot methods, evaluated its influence on the growth of PANC-1 cells by apoptosis detection, growth curve, and flow cytometry. RESULTS: Our results showed that the DNAzyme digested mRNA substrates of survivin efficiently in a dosage- and time-dependent manner, markedly increased apoptosis and inhibited the growth of human pancreatic carcinoma cell line PANC-1, compared with the disabled DNAzyme and untreated controls. CONCLUSIONS: Our results showed that the designed DNAzyme against survivin mRNA is a good candidate for cancer gene therapy of human pancreatic carcinoma.

Apoptosis↗