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Biomedical subjects

Jie Li

Publications and source records attributed to Jie Li.

At least 235 records · Page 13Linked to original sources

[Inhibitory effect of antisense and dominant-negative AKT2 constructs on proliferation of glioma cell line TJ905].

BACKGROUND & OBJECTIVE: Serine/threonine kinase (AKT) mediates a downstream signal transduction pathway of epidermal growth factor receptor (EGFR), and plays an important role in survival and apoptosis of tumor cells. This study was designed to investigate regulation of antisense AKT2 (AS-AKT2) and dominant-negative AKT2 (DN-AKT2) constructs on proliferation and apoptosis of glioma cell line TJ905. METHODS: AS-AKT2 and DN-AKT2 were transfected into TJ905 cells, 3 stably transfected clones were randomly selected from each group, and amplified for further study. The expression of AKT2 was detected by in situ hybridization and Western blot. Proliferation rate of TJ905 cells was evaluated by MTT assay and Ki67 labeling index (Ki67 LI), cell apoptosis was detected by TUNEL method. RESULTS: AKT2 expression was significantly inhibited in TJ905 cells transfected with AS-AKT2, while no significant change observed in TJ905 cells transfected with DN-AKT2. Compared with parental TJ905 cells and TJ905 cells transfected with empty vector, the 6-day survival rates of TJ905 cells transfected with AS-AKT2, and DN-AKT2 dramatically dropped to 49.3%-51.5%, and 50.5%-55.2% (P< 0.001). The Ki67 LI of TJ905 cells transfected with AS-AKT2, and DN-AKT2 dropped to 57.5%-59.3% and 59.2%-61.0%, lower than those of parental TJ905 cells (76.5%), and TJ905 cells transfected with empty vector (74.8%) (P < 0.05). Nearly no apoptotic cells found in parental TJ905 cells or TJ905 cells transfected with empty vector, however, apoptosis indexes (AIs) of TJ905 cells transfected with AS-AKT2, and DN-AKT2 prominently increased to 8.8%-8.5%, and 7.5%-7.8% (P< 0.05). The inhibitory effect of AS-AKT2 on cell growth was statistically stronger than that of DN-AKT2 (P< 0.001), while no difference was detected in Ki67 LI and AI between AS-AKT2 and DN-AKT2 transfected TJ905 cells. CONCLUSION: AKT2 pathway may modulate proliferation and apoptosis of glioma cells, indicating that it may be a potential therapeutic target of gene therapy of malignant glioma.

Apoptosis↗

Anemia in patients on combined androgen block therapy for prostate cancer.

AIM: To study the effect of combined androgen block therapy on hemoglobin and hematocrit values in patients with prostate cancer. METHODS: One hundred and thirty-six patients with adenocarcinoma of prostate were treated with combined androgen block (orchiectomy and flutamide 250 mg, tid). Complete blood counts were determined before and after 1, 2, 3, 6, 9 and 12 months of therapy. RESULTS: The hemoglobin and hematocrit levels declined significantly in all patients and at all the time points after treatment (P<0.05). CONCLUSION: Prostate cancer patients treated with combined androgen block would develop obvious anemia. Recombinant human erythropoietin can be used to treat patients with severe anemia.

Adenocarcinoma↗

Plasma induced degradation of Indigo Carmine by bipolar pulsed dielectric barrier discharge(DBD) in the water-air mixture.

Degradation of the Indigo Carmine (IC) by the bipolar pulsed DBD in water-air mixture was studied. Effects of various parameters such as gas flow rate, solution conductivity, pulse repetitive rate and ect., on color removal efficiency of dying wastewater were investigated. Concentrations of gas phase o3 and aqueous phase H2O2 under various conditions were measured. Experimental results showed that air bubbling facilitates the breakdown of water and promotes generation of chemically active species. Color removal efficiency of IC solution can be greatly improved by the air aeration under various solution conductivities. Decolorization efficiency increases with the increase of the gas flow rate, and decreases with the increase of the initial solution conductivity. A higher pulse repetitive rate and a larger pulse capacitor C(p) are favorable for the decolorization process. Ozone and hydrogen peroxide formed decreases with the increase of initial solution conductivity. In addition, preliminary analysis of the decolorization mechanisms is given.

Air↗

[Effects of ketamine-midazolam anesthesia on focal cerebral ischemic injury in rats].

OBJECTIVE: To compare the effects of anesthesia with ketamine and ketamine-midazolam on focal cerebral ischemic injury in rats and evaluate the neuroprotective effect of ketamine-midazolam anesthesia during surgical procedures. METHODS: Thirty male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) under anesthesia with intraperitoneal administration of ketamine alone or in combination with midazolam (n=15). Neurological scoring was conducted the infarct size measured at 4 h and 24 h after the surgery. Histological examination was performed using TUNEL staining 72 h after MCAO. RESULTS: After MCAO, the neurological scores showed no significant difference between ketamine and ketamine-midazolam groups (1.57+/-0.65 vs 1.74+/-0.52, P>0.05), but the rats in the latter group had significantly smaller infarct size (38.48/+/-4.18/ vs 24.1/+/-4.63/, P<0.05) and lower apoptotic cell density (258+/-15 cells/mm2 vs 178+/-23 cells/mm2, P<0.05) in the penumbra. CONCLUSION: Compared with ketamine used alone, anesthesia with the combination of ketamine and midazolam may provide neuroprotection from ischemic cerebral injury by reducing the infarct size and lowering the cell apoptosis rate following MCAO in rats.

Adjuvants, Anesthesia↗

[Analysis of codon usage in potato and its application in the modification of t-PA gene].

Bioperl-1.0 was used under Hongqi LINUX system to program the codon analysis software. According to the analysis of 98 codon DNA sequences with this software, the codon usage in potato was calculated and 4 codons have been inferred to the optimal codons. The codons of tissue plasminogen activator (t-PA) gene sequence have been reconstructed according to the results. The t-PA gene sequence containing the optimal codons of potato will be used for t-PA production by potato bioreactor.

Amino Acid Sequence↗

[Comparison of pentobarbital and propofol on the outcome of focal cerebral ischemia model in rats].

OBJECTIVE: To compare the effects of pentobarbital and propofol on the outcome of focal cerebral ischemia model, and to evaluate the availability of propofol in setting the focal cerebral ischemia. METHODS: Thirty male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) under pentobarbital or propofol intraperitoneal anesthesia (n=15 each). A modified Bederson's scoring system was adopted to assess neurological scoring at 4 h after the MCAO. TTC staining was used to determine the infarct size at 24 h after the MCAO. At day 3 after the MCAO, TUNEL and toluidine blue staining were performed to measure the density of apoptotic cells and surviving neurons in the penumbra. RESULTS: Neither neurological scoring (1.46 +/- 0.98 vs 1. 29 +/- 0.72), infarct size [(37.8 +/- 4.95)% vs (31.1 +/- 5.09)%] nor neuronal density in the penumbra [(740 +/- 24) neurons/mm2 vs (794 +/- 23) neurons/mm2] was statistically different between pentobarbital and propofol groups (P > 0.05). But apoptotic cell density in the penumbra was significantly higher in the propofol group than that in the pentobarbital group [(356 +/- 20) cells/mm2 vs (262 +/- 17) cells/mm2, P < 0.05]. CONCLUSION: In the establishment of the focal ischemia model in rats, anesthesia with propofol or pentobarbital induces similar neurological scoring, infarct size and survived neurons in the penumbra. Propofol anesthesia increases cell apoptosis in the penumbra compared with pentobarbital and its application might be an unsuitable anesthetic method in the model for evaluating the effect of procedures or drugs on cell apoptosis.

Adjuvants, Anesthesia↗

Reduced inflammatory mediator expression by pre-reperfusion infusion into ischemic territory in rats: a real-time polymerase chain reaction analysis.

The aim in this study was to investigate if our new experimental model for stroke therapy, flushing the ischemic territory with saline prior to reperfusion, could reduce overexpression of inflammatory mediators during reperfusion. Stroke in Sprague-Dawley rats (n=24) was induced by a 2-h middle cerebral artery occlusion using a novel intraluminal hollow filament. Prior to reperfusion, 12 of the ischemic rats received 6 ml isotonic saline at 37 degrees C infused into the ischemic area through the filament. Expression of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecule 1 (ICAM-1) mRNA was analyzed by real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR). A significant overexpression (9-26 fold) of the genes encoding TNF-alpha, IL-1beta and ICAM-1 in ischemic rats was found during early reperfusion without flushing at 6 and 12 h. This increase was significantly reduced at both 6 and 12 h post-reperfusion as a result of saline flushing.

Animals↗

Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke.

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke. The goal of this study was to determine if cerebral local cooling infusion could reduce stroke-mediated brain injury by inhibiting inflammatory responses. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h reperfusion. This cold saline infusion significantly ( P<0.01) reduced temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1 degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to 33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after reperfusion. Consequently, significant ( P<0.01) reductions in endothelial expression of intracellular adhesion molecule-1 (ICAM-1), the key step for inflammatory progress, as well as leukocyte infiltration, were evident in both cortex and striatum after reperfusion. As a control, ischemic rats received the same amount of cold saline systemically through a femoral artery. A mild hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to normal within 5 min. Brain temperature in ischemic rats perfused locally with saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and accumulation of leukocytes was observed in ischemic control groups without brain cooling infusion. In conclusion, brain hypothermia induced by local pre-reperfusion infusion ameliorated brain inflammation from stroke.

Analysis of Variance↗

Emerging role for autophagy in the removal of aggresomes in Schwann cells.

The presence of protein aggregates in the nervous system is associated with various pathological conditions, yet their contribution to disease mechanisms is poorly understood. One type of aggregate, the aggresome, accumulates misfolded proteins destined for degradation by the ubiquitin-proteasome pathway. Peripheral myelin protein 22 (PMP22) is a short-lived Schwann cell (SC) protein that forms aggresomes when the proteasome is inhibited or the protein is overexpressed. Duplication, deletion, or point mutations in PMP22 are associated with a host of demyelinating peripheral neuropathies, suggesting that, for normal SC cell function, the levels of PMP22 must be tightly regulated. Therefore, we speculate that mutant, misfolded PMP22 might overload the proteasome and promote aggresome formation. To test this, sciatic nerves of Trembler J (TrJ) neuropathy mice carrying a leucine-to-proline mutation in PMP22 were studied. In TrJ neuropathy nerves, PMP22 has an extended half-life and forms aggresome-like structures that are surrounded by molecular chaperones and lysosomes. On the basis of these characteristics, we hypothesized that PMP22 aggresomes are transitory, linking the proteasomal and lysosomal protein degradation pathways. Here we show that Schwann cells have the ability to eliminate aggresomes by a mechanism that is enhanced when autophagy is activated and is primarily prevented when autophagy is inhibited. This mechanism of aggresome clearance is not unique to peripheral glia, because L fibroblasts were also capable of removing aggresomes. Our results provide evidence for the involvement of the proteasome pathway in TrJ neuropathy and for the role of autophagy in the clearance of aggresomes.

Animals↗

New anti-malarial peroxides with in vivo potency derived from spongean metabolites.

The structure-activity relationship of the anti-malarial substance 3 having a 6-carbomethoxymethyl-3-methoxy-1,2-dioxane structure was studied. The ester portion of the peroxide 3, showing little in vivo efficacy in malaria-infected mice in spite of the potent in vitro activity, was hydrolyzed in serum to afford an inactive free acid 4. The amide analogues (8 and 9) robust to mouse serum were disclosed to exhibit in vivo anti-malarial potency.

Animals↗

Positional cloning of the major quantitative trait locus underlying lung tumor susceptibility in mice.

Pulmonary adenoma susceptibility 1 (Pas1), located on chromosome 6, is the major locus affecting inherited predisposition to lung tumor development in mice. We have fine mapped the Pas1 locus to a region of approximately 0.5 megabases by using congenic strains of mice, constructed by placing the Pas1 region of chromosome 6 from A/J mice onto the genetic background of C57BL/6J mice. Systematic characterization of Pas1 candidates establishes the Las1 (lung adenoma susceptibility 1) and Kras2 (Kirsten rat sarcoma oncogene 2) genes as primary candidates for the Pas1 locus. Clearly, Kras2 affects lung tumor progression only, and Las1 is likely to affect lung tumor multiplicity.

Adenoma↗

The association of alpha-synuclein with membranes affects bilayer structure, stability, and fibril formation.

The aggregation of alpha-synuclein is believed to be a critical factor in the etiology of Parkinson's disease. alpha-Synuclein is an abundant neuronal protein of unknown function, which is enriched in the presynaptic terminals of neurons. Although alpha-synuclein is found predominantly in the cytosolic fractions, membrane-bound alpha-synuclein has been suggested to play an important role in fibril formation. The effects of alpha-synuclein on lipid bilayers of different compositions were determined using fluorescent environment-specific probes located at various depths. alpha-Synuclein-membrane interactions were found to affect both protein and membrane properties. Our results indicate that in addition to electrostatic interactions, hydrophobic interactions are important in the association of the protein with the bilayer, and lead to disruption of the membrane. The latter was observed by atomic force microscopy and fluorescent dye leakage from vesicles. The kinetics of alpha-synuclein fibril formation were significantly affected by the protein association and subsequent membrane disruption, and reflected the conformation of alpha-synuclein. The ability of alpha-synuclein to disrupt membranes correlated with the binding affinity of alpha-synuclein for the particular membrane composition, and to the induced helical conformation of alpha-synuclein. Protofibrillar or fibrillar alpha-synuclein caused a much more rapid destruction of the membrane than soluble monomeric alpha-synuclein, indicating that protofibrils (oligomers) or fibrils are likely to be significantly neurotoxic.

2-Naphthylamine↗

PRL-3 and PRL-1 promote cell migration, invasion, and metastasis.

We demonstrate here that Chinese hamster ovary cells stably expressing PRL-3, a M(r) 20000 prenylated protein tyrosine phosphatase, or its relative, PRL-1, exhibit enhanced motility and invasive activity. A catalytically inactive PRL-3 mutant has significantly reduced migration-promoting activity. We observe that PRL-3 is associated with diverse membrane structures involved in cell movement. Furthermore, we show that PRL-3- and -1-expressing cells, but not control cells, induce metastatic tumor formation in mice. Thus, our results deliver the first evidence for a causative role of PRL-3 and -1 in promoting cell motility, invasion activity, and metastasis.

Animals↗

[The clinical characteristics and outcome of 45 early stage patients with SARS].

OBJECTIVE: To investigate the clinical characteristics and therapeutic effect in the early stage of patients with Severe Acute Respiratory Syndrome (SARS). METHODS: A total of 45 clinical diagnosed SARS patients were enrolled in the study. RESULTS: 43 (95.6%) of all 45 patients had exposure to SARS patients and the average incubation time was (7.3 +/- 4.7) days (range 2 to 20 days). The clinical features including fatigue (60%), dry cough (68.9%), dyspnea (53.3%), joint pain (26.7%) and diarrhea (26.7%). The laboratory test show that 33% patients with leukopenia and thrombocytopenia, 53.3% with elevated serum aminotransferase and 26.6% with increased creatinine kinase levels. The occurrence of abnormal chest radiographs was (4.2 +/- 2.9) days from the onset, and CT scanning was better than X-ray in the early diagnosis. The average time for the progression and improvement of the chest radiographs were (9.3 +/- 4.1) and (14.5 +/- 5.0) days, respectively. The administration of corticosteroids was started (4.8 +/- 3.5) days from the onset and the maximal dosage using of steroids was (8.4 +/- 3.9) days. There was a significant difference in the dosage of steroid between severe and mild patients [(610.6 +/- 212.4) mg/day vs (268.1 +/- 202.5) mg/day, P < 0.001)]. The IgG antibody was detected in 22 out of 34 (64.7%) patients and the average time for the occurrence of antibody was (18.2 +/- 6.4) days (range 9-27 days). CONCLUSION: Exposure to the SARS patients happened in most patients. The most common clinical features were fever and fatigue. The most common laboratory abnormalities were leukopenia and thrombocytopenia. Serum antibody was not detected until on the 9th day of the course of illness; CT is a more sensitive method for detection of the abnormal chest radiographs than regular X-ray test. The early usage of cortiscosteroids was an efficient method for the treatment, and the dosage of steroids should be individualized.

Adrenal Cortex Hormones↗

[Primary investigation on the changing mode of plasma specific IgG antibody in SARS patients and their physicians and nurses].

OBJECTIVES: To primarily investigate the changing mode of anti-SARS coronavirus IgG antibody in clinically diagnosed SARS patients and the possibility of subclinical infection in physicians and nurses through close association with SARS patients. METHODS: The plasma levels of anti-SARS coronavirus IgG antibody of 57 normal subjects, 127 physicians and nurses worked in SARS wards for one month and 73 SARS patients with different course of SARS were measured by enzyme linked immunosorbent assay. RESULTS: Plasma anti-SARS coronavirus IgG antibody was not detected in normal subjects and the clinical personnel. After 0-7 days, 8-10 days, 11-14 days, 15-20 days of onset of disease, the positive rates were 0.33%, 52%, 86% respectively, and the general positive rate was 61%. CONCLUSION: The specificity and sensitivity of ELISA to detect plasma anti-SARS IgG antibody were satisfactory. Cases with positive reaction could be diagnosed as patients already infected by the virus. The specific IgG antibody didn't emerge in some patients in the early stage of the disease, and the negative results didn't indicate that they were not infected. And follow-up investigation should be made in those patients. Unlike common epidemic infectious diseases, SARS probably hadn't the potentiality of subclinical infection.

Adult↗