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Jing Yang

Publications and source records attributed to Jing Yang.

At least 55 records · Page 3Linked to original sources
PubMed2006

Selection of antisense oligonucleotides based on multiple predicted target mRNA structures.

BACKGROUND: Local structures of target mRNAs play a significant role in determining the efficacies of antisense oligonucleotides (ODNs), but some structure-based target site selection methods are limited by uncertainties in RNA secondary structure prediction. If all the predicted structures of a given mRNA within a certain energy limit could be used simultaneously, target site selection would obviously be improved in both reliability and efficiency. In this study, some key problems in ODN target selection on the basis of multiple predicted target mRNA structures are systematically discussed. RESULTS: Two methods were considered for merging topologically different RNA structures into integrated representations. Several parameters were derived to characterize local target site structures. Statistical analysis on a dataset with 448 ODNs against 28 different mRNAs revealed 9 features quantitatively associated with efficacy. Features of structural consistency seemed to be more highly correlated with efficacy than indices of the proportion of bases in single-stranded or double-stranded regions. The local structures of the target site 5' and 3' termini were also shown to be important in target selection. Neural network efficacy predictors using these features, defined on integrated structures as inputs, performed well in "minus-one-gene" cross-validation experiments. CONCLUSION: Topologically different target mRNA structures can be merged into integrated representations and then used in computer-aided ODN design. The results of this paper imply that some features characterizing multiple predicted target site structures can be used to predict ODN efficacy.

Algorithms↗
PubMed2006

Long-term metformin treatment stimulates cardiomyocyte glucose transport through an AMP-activated protein kinase-dependent reduction in GLUT4 endocytosis.

Long-term (18 h) metformin treatment of cardiomyocytes increased glucose transport activity 3- to 5-fold, as measured using the phosphorylated sugar 2-deoxy-D-glucose and the nonphosphorylated sugar 3-O-methyl-D-glucose. The affinity for 3-O-methyl-D-glucose transport was not increased by metformin treatment. Total levels of glucose transporter 4 (GLUT4) were not changed by 18-h culture with or without insulin or metformin treatment. GLUT1 levels were elevated after 18 h in culture, but this increase was not altered by insulin or metformin treatment. Metformin-induced stimulation of transport was not inhibited by treatment with wortmannin and was additive with that of insulin. These data suggest that the metformin effect is mediated by a signaling route independent of phosphatidylinositol 3-kinase and Akt. Surprisingly, however, levels of both phospho-AMP-activated protein kinase and phospho-Akt were increased 4- and 3-fold, respectively, after metformin treatment. Chronic treatment with insulin for 18 h led to down-regulation of insulin-stimulated glucose transport. Cotreatment with metformin bypassed this insulin resistance by maintaining high transport levels. These data also indicate an independent point of convergence of metformin and insulin stimuli on GLUT4 regulatory processes. To test the possibility of altered GLUT4 subcellular trafficking, the kinetics of GLUT4 exocytosis and endocytosis were determined. Metformin treatment markedly slowed endocytosis of GLUT4, but exocytosis was not increased. We conclude that metformin treatment leads to a longer residence time of GLUT4 in the plasma membrane due to an AMP-activated protein kinase-dependent reduction in endocytosis. This accounts for metformin's ability to enhance hexose transport activity above insulin-stimulated and Akt-dependent levels.

AMP-Activated Protein Kinases↗
PubMed2006

Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

Epidemiological studies indicate that the intake of flavonoids is inversely associated with risk of stroke, cardiovascular diseases and cancer. Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet, anti-tumor, anti-allergic, antiviral activities and estrogenic properties. However, there is no report on the effects of ISL in cerebral ischemia. Evidence demonstrate that the impaired energy metabolism and the excessive generation of reactive oxygen radicals (ROS) contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effects of ISL were investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-pretreated group, and three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were administered once a day, for 7 days prior to ischemia. The rats were subjected to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion. Pretreatment with ISL significantly reduced the cerebral infarct volume and edema and produced significant reduction in neurological deficits. In this study, in order to clarify the mechanism of ISL's protection against cerebral ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity, malondialdehyde (MDA) content and antioxidant enzyme activities were measured. ISL pretreatment increased the brain ATP content, energy charge (EC) and total adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase activity was protected significantly by pretreatment of ISL for 7 days. Pretreatment with ISL significantly inhibited the increases of brain MDA content and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) from declines caused by cerebral ischemia-reperfusion. All these findings indicate that ISL has the protective potential against cerebral ischemia injury and its protective effects may be due to the amelioration of cerebral energy metabolism and its antioxidant property.

Adenine Nucleotides↗
PubMed2006

Influence of various central moieties on the hypolipidemic properties of long hydrocarbon chain diols and diacids.

A series of long (11-15) hydrocarbon chain diols and diacids with various central functional groups and terminal gem-dimethyl or -methyl/aryl substituents was synthesized and evaluated in both in vivo and in vitro assays for its potential to favorably alter lipid disorders including metabolic syndrome. Compounds were assessed for their effects on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, as well as for their effects on lipid and glycemic variables in obese female Zucker fatty rats, Crl:(ZUC)-faBR. The most active compounds were hydroxyl-substituted symmetrical diacids and diols with a 13-atom chain and terminal gem-dimethyl substituents. Furthermore, biological activity was enhanced by central substitution with O, C=O, S, S=O compared to the methylene analogues and was diminished for compounds with central functional groups such as carbamate, ester, urea, acetylmethylene, and hydroxymethylene.

Administration, Oral↗
PubMed2006

AOBase: a database for antisense oligonucleotides selection and design.

Antisense oligonucleotides (ODNs) technology is one of the important approaches for the sequence-specific knockdown of gene expression. ODNs have been used as research tools in the post-genome era, as well as new types of therapeutic agents. Since finding effective target sites within RNA is a hard work for antisense ODNs design, various experimental methods and computational approaches have been proposed. For better sharing of the experimented and published ODNs, valid and invalid ODNs reported in literatures are screened, collected and stored in AOBase. Till now, approximately 700 ODNs against 46 target mRNAs are contained in AOBase. Entries can be explored via TargetSearch and AOSearch web retrieval interfaces. AOBase can not only be useful in ODNs selection for gene function exploration, but also contribute to mining rules and developing algorithms for rational ODNs design. AOBase is freely accessible via http://www.bioit.org.cn/ao/aobase.

Algorithms↗
PubMed2006

Gene-chip analysis of the effect of tripeptide tyroservatide (YSV) on gene-expression in human hepatocarcinoma BEL-7402 tumors transplanted to nude mice.

Tyroservatide (YSV) is a bioactive tripeptide of tyrosyl-seryl-valine. In this study, we studied the effects of YSV on human hepatocarcinoma BEL-7402 tumors transplanted in BALB/c (nu/nu) nude mice, and gene expression in the tumor cells with gene-chip analysis. Results show that YSV significantly inhibits the growth of transplanted human hepatocarcinoma BEL-7402 in nude mice (n = 12) compared with the control group (P < 0.05); with an inhibition rate of 55% at 320 microg/kg/d. Seven hundred eighty-one genes were different between the YSV group and the control group. Fifty-two genes changed in expression level by onefold or more including 37 downregulated genes and 15 upregulated genes. Probably, YSV exhibits a significant antitumor activity by inhibiting the expression of tumor cells histone genes, then damaging tumor cell chromosome and killing tumor cells.

Animals↗
PubMed2006

Construction of eukaryotic expressing plasmids encoding HA and HA1 of influenza A virus and their transient expression in HEK293 cells.

In order to explore the feasibility and protective efficiency of influenza DNA vaccine, we constructed eukaryotic expressing plasmids encoding HA and HA1 of influenza A virus (A/PR/8/34) and studied their expression in HEK293 cells. HA and HA1 genes were amplified by RT-PCR and cloned into pcDNA3.1(+) to generate pcDNA3.1(+)/HA and pcDNA3.1(+)/HA1, respectively. After verification of the cloning fidelity by restriction endonuclease digestion, PCR, and sequencing, pcDNA3.1(+)/HA and pcDNA3.1(+)/HA1 were transfected into HEK293 cells using PolyFect Transfection Reagent. Immunofluorescence assay was used to detect the transient expressing cells. Fluorescence microscopy revealed strong expression of target gene in HEK293 cells transiently transfected with either pcDNA3.1(+)/HA or pcDNA3.1(+)/HA1. Therefore, the results confirm the successful construction of eukaryotic expressing plasmids capable of driving the eukaryotic expression of influenza virus antigen HA and HA1, which is likely to provide a basis for both further investigation of the mechanism of influenza viral infection and the development of influenza DNA vaccine.

Cell Line↗
PubMed2006

Targeting beta2-microglobulin for induction of tumor apoptosis in human hematological malignancies.

We discovered that monoclonal antibodies (mAbs) specific to human beta(2)-microglobulin (beta(2)M) induce apoptosis in vitro and were therapeutic in mouse models of myeloma and other hematological tumor cells. Cell death occurred rapidly, without the need for exogenous immunological effector mechanisms. The mAbs induced cell death via recruiting MHC class I molecules to lipid rafts and activating Lyn and PLCgamma2, leading to activated JNK and inhibited PI3K/Akt and ERK, compromised mitochondrial integrity, and caspase-9-dependent cascade activation. Although the expression of beta(2)M on normal hematopoietic cells is a potential safety concern, the mAbs were selective to tumor-transformed cells and did not induce apoptosis of normal cells. Therefore, such mAbs offer the potential for a therapeutic approach to hematological malignancies.

Animals↗
PubMed2006

Microarray analysis of differentially expressed genes in mouse bone marrow tissues after ionizing radiation.

PURPOSE: To identify differentially expressed genes in mouse bone marrow involved in radiation-induced injury. MATERIALS AND METHODS: Microarray analysis was used to identify the differentially expressed genes and other techniques, e.g., polymerase chain reaction (PCR), western-blotting and antisense were also used to validate the results. RESULTS: DNA microarray analysis demonstrated that the mRNA of 34 genes increased and 69 genes decreased in mouse bone marrow cells (BMC) from C57BL mice 6 h after a whole body dose of 6.5 Gy. These differentially expressed genes were involved in a number of processes including DNA replication/repair, proliferation/apoptosis, cell cycle control and RNA processing. In these experiments, a decline of the mammalian homolog Sir2a (an acronym for the silent mating type information regulation 2 homolog [SIRT1]) mRNA accompanied by an increase of P53 protein acetylation was observed in irradiated BMC. To determine whether the reduced SIRT1 is related to the higher acetylation status of P53 after irradiation, we designed and synthesized antisense oligonucleotides (AS) targeting human SIRT1 mRNA. Notably, AS transfection increased tumor protein 53 (P53) protein acetylation and bax-luciferase activity in human bone marrow stromal cell line (HS-5) after radiation. Furthermore, the AS transfer stimulated cell apoptosis in post-irradiation HS-5 cells. CONCLUSION: Ionizing radiation (IR) affects the expression of a series of genes including genes involved in G1/S transition and the P53 pathway. Among those, reduction of SIRT1 was seen to be involved in transactivation of P53.

Animals↗
PubMed2006

Exploring the molecular basis of tumor metastasis by microarray analysis.

Over the past decade, microarray technology has become a powerful tool to provide a genome-wide view of genetic or epigenetic changes associated with tumor metastasis. To extract biologically meaningful information from the vast amounts of microarray data, it is crucial to choose suitable biological systems and have vigilant experimental design. In this review, I will discuss several experimental systems that are used to identify genes involved in tumor metastasis by microarray analysis. Also highlighted are the pros and cons for each system. In particular, I will describe our experience of using microarray technology to identify the transcription factor Twist as an essential player in tumor metastasis.

Animals↗
PubMed2006

Reproductive outcome of septate uterus after hysteroscopic treatment with neodymium:YAG laser.

OBJECTIVE: The aim of this study was to assess fertility outcome and obstetrical prognosis of 46 patients after hysteroscopic section of uterine septa with neodysmium:yttrium-aluminum-garnet (Nd:YAG) laser. BACKGROUND DATA: Approximately 15-25% of spontaneous miscarriages are related to Müllerian fusion defects, most of which are associated with uterine septa. Operative hysteroscopy is a safe and effective treatment for uterine septa. METHODS: Forty-six sterile patients with septate uterus received hysteroscopic metroplasty with Nd:YAG laser. Forty-one patients with incomplete septate uterus were under the guidance of B-ultrasonography, while the other 5 patients with complete septate uterus were treated by laparoscopy. RESULTS: The metroplasty was successfully conducted in 45 patients, with a success rate of 98% (45 /46). Postoperative follow-up examinations of 28 patients revealed pregnancy within 12 months in 20 patients, 16 of whom acquired term delivery. The pregnancy rate within 1 year was 71%. CONCLUSION: Hysteroscopic treatment of septate uterus with Nd:YAG laser is effective. The cervix may not be excessively dilated, the intraoperative bleeding can be thoroughly controlled, and the procedure under local anesthesia is relatively safe.

Adult↗
PubMed2006

Event-related potential N270 in detecting cognitive impairment in patients with transient ischemic attack.

Latency and amplitude of the visual P300 and N270 were examined in patients with transient ischemic attack (TIA) and in age-matched healthy control subjects to investigate the feasibility of N270 as a clinical examination method to evaluate the cognitive status of patients with TIA. Stimulus pairs with identical (match condition) or different (conflict condition) colors were randomly presented to subjects. Each pair consisted of two sequential stimuli (S1 and S2) that lasted for 300 ms; the onset interval between them was 700 ms. Thirty TIA patients without clinical dementia and 30 age-matched control subjects determined if the two stimuli in a pair had the same color. Subjects were required to press a button in the match condition and another button in the conflict condition. Event-related potentials (ERPs) were recorded from their scalp electrodes at the same time. N270 was evoked by the second stimulus (S2) of the conflict condition in either control subjects or patients. The patient group exhibited a delayed N270 than the control group. TIA patients as a group showed cognitive decline. N270 is an effective index to detect the cognitive impairment of TIA patients.

Adult↗
PubMed2006

Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-alpha secretion, abnormal calcium cycling, and cardiac dysfunction in rats.

AIM: To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor alpha (TNF-alpha) release, and intracellular calcium concentration ([Ca(2+)]i) in cardiomyocytes exposed to lipopolysaccharide (LPS). METHODS: Primary cultured rat cardiomyocytes were prepared from ventricles of 3-4-day old Sprague-Dawley rats. TNF-alpha concentrations in cell-conditioned media were measured by using a Quantikine enzyme-linked immunosorbent assay kit, and cardiomyocyte [Ca(2+)]i was measured by using Fura-2/AM. The isolated rat hearts were perfused in the Langendorff mode. RESULTS: LPS at doses of 1, 5, 10, and 20 microg/mL markedly stimulated TNF-alpha secretion from cardiomyocytes, and neutral sulfate berberine inhibited LPS-induced TNF-alpha production. Intracellular calcium concentration was significantly decreased after LPS stimulation for 1 h, and increased 2 h after LPS treatment. Pretreatment with neutral sulfate berberine reversed the LPS-induced [Ca(2+)]i alterations, although neutral sulfate berberine did not inhibit a rapid increase in cardiomyocyte [Ca(2+)]i induced by LPS. Perfusion of isolated hearts with LPS (100 microg/mL) for 20 min resulted in significantly impaired cardiac performance at 120 min after LPS challenge: the maximal rate of left ventricular pressure rise and fall (+/-dp/dt(max)) decreased compared with the control. In contrast, +/-dp/dt(max) at 120 min in hearts perfused with neutral sulfate berberine (1 micromol/L) for 10 min followed by 20 min LPS (100 microg/mL) was greater than the corresponding value in the LPS group. CONCLUSION: Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-alpha production, impairs calcium cycling, and improves LPS-induced contractile dysfunction in intact heart.

Animals↗
PubMed2006

Metallothionein mediates cardioprotection of isoliquiritigenin against ischemia-reperfusion through JAK2/STAT3 activation.

AIM: To examine whether isoliquiritigenin (ISL) can attenuate myocardial ischemiareperfusion (MI/R) injury in rats by inducing metallothionein (MT) through activation of janus kinase 2 (JAK 2)/signal transducers and activators of transcription 3 (STAT 3) pathway. METHODS: The experimental model of MI/R in rats was generated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX-2, and iNOS were measured by RT-PCR. The protein expressions of MT, JAK/STAT, extracellular signal-regulated kinase (ERK), and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 (1.0 mg/kg, iv, 1 h before ischemia). RESULTS: Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation. CONCLUSION: ISL protected MI/R injury through activation of JAK 2/STAT 3 signal transduction pathway, which might be involved in mediating the upregulation of MT expression.

Animals↗
PubMed2006

Cortical neuronal and glial pathology in TgTauP301L transgenic mice: neuronal degeneration, memory disturbance, and phenotypic variation.

Recapitulation of tau pathologies in an animal model has been a long-standing goal in neurodegenerative disease research. We generated transgenic (TgTauP301L) mice expressing a frontotemporal dementia with parkinsonism linked to chromosome 17 (FTPD-17) mutation within the longest form of tau (2N, 4R). TgTauP301L mice developed florid pathology including neuronal pretangles, numerous Gallyas-Braak-positive neurofibrillary tangles, and glial fibrillary tangles in the frontotemporal areas of the cerebrum, in the brainstem, and to a lesser extent in the spinal cord. These features were accompanied by gliosis, neuronal loss, and cerebral atrophy. Accumulated tau was hyperphosphorylated, conformationally changed, ubiquitinated, and sarkosyl-insoluble, with electron microscopy demonstrating wavy filaments. Aged TgTauP301L mice exhibited impairment in hippocampally dependent and independent behavioral paradigms, with impairments closely related to the presence of tau pathologies and levels of insoluble tau protein. We conclude that TgTauP301L mice recreate the substantial phenotypic variation and spectrum of pathologies seen in FTDP-17 patients. Identification of genetic and/or environmental factors modifying the tau phenotype in these mice may shed light on factors modulating human tauopathies. These transgenic mice may aid therapeutic development for FTDP-17 and other diseases featuring accumulations of four-repeat tau, such as Alzheimer's disease, corticobasal degeneration, and progressive supranuclear palsy.

Animals↗
PubMed2006

[Analysis of the secreted proteins encoded by genes in genome of filamental fungus (Neurospora crassa)].

The completed genome sequence of filamental fungus Neurospora crassa has completed and 10,082 open reading frames (ORFs) were predicted in whole genome. Among them, 437 proteins were secreted ones based on the combination of prediction algorithms SignalP v3.0 and PSORT, transmembrane domains prediction algorithms TMHMM v2.0 and THUMBUP, potential GPI-anchor sites prediction algorithm big-PI predictor and the subcellular protein location prediction algorithm TargetP v1.01. The minimum ORF length of the encoding sequences for 437 secreted proteins was 252 bp, the maximum ORF length was 6 604 bp and average was 1 433 bp. The length of signal peptide of secreted proteins ranged from 15 to 59 amino acids. Among the 437 secreted proteins, 205 were provided with function description. The function of secretory proteins were involved in kinds of enzyme, cell energy, transmission, cell recovered itself and defense mechanism et al. These results implied that processes catalyzed by these proteins probably occurred outside of cells, at least partially.

Amino Acid Sequence↗
PubMed2006

[Expression of caspase-8 after brain injury from fluid percussion in rats].

OBJECTIVE: To provide the evidence of the relationship between brain injury and the time of injury. METHODS: Rats were contused on brain by fluid percussion, then were killed after injury for 15 min, 30 min, 1,3,6,12 h, and 1,4,7,14 d respectively. The expression of caspase-8 were detected by immunohistochemical technology on rat brain section and the results were assessed by image analysis system in the cerebral cortex, thalamus, and hippocampus. RESULTS: The expression of caspase-8 in cortex and hippocampus could be detected in 30 min after injury, increased significantly in 3h, reached apex in 1d after injury, remained 4d before decreased. In addition, the expression of caspase-8 can be detected in 1h after injury and reached apex in 1d after injury, and remained 4d then reduced. CONCLUSION: It seems that the expression of caspase-8 should be a useful target for diagnosis of early brain injury.

Animals↗