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Peng Li

Publications and source records attributed to Peng Li.

At least 127 records · Page 7Linked to original sources
PubMed2004

Role of urokinase plasminogen activator and its receptor in metastasis and invasion of neuroblastoma.

BACKGROUND/PURPOSE: Urokinase plasminogen activator (uPA) is a serine proteinase that has been suggested to play an important role in tumor invasion and metastasis. It binds to a specific membrane receptor, uPA receptor (uPAR), and activates plasminogen to form plasmin, which participates in tissue degradation and proteolysis. Binding of uPA to its receptor accelerates the activation of uPA from pro-uPA, enhancing the activity of the uPA/uPAR cascade. Because of the high metastatic and invasive potential of neuroblastoma (NB) cells, the authors have analyzed in the current study, the concomitant of uPA and its receptor in NB. METHODS: The expression and distribution of uPA and uPAR were analyzed by immunostaining in 52 neuroblastoma tissues; at the same time we use the reverse transcriptase polymerase chain reaction (RT-PCR) for neuroendocrine protein gene products 9.5 (PGP 9.5) mRNA to detect small numbers of NB cells in the peripheral blood and bone marrow (BM) and study the relationship uPA and uPAR to the ability of invasion and metastasis of NB cells. To identify risk factors for disease progression, the authors performed a retrospective analysis of clinical (age, sex, and risk group) and tumor biologic markers (histology, MYCN, DNA ploidy, chromosome 1 p, PGP9.5, uPA, uPAR, and combined uPA and uPAR) in all patients. Survival curves were estimated using the Kaplan-Meier method. Univariate analysis was performed with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The results of immunohistochemistry showed that uPA and uPAR were localized mainly in the membrane and cytoplasm of tumor cells. The positive rate of uPA in the high-risk group (23 of 25, 92.0%) was remarkably higher than that in intermediate-risk group (8 of 17, 47.1%) and low-risk group (3 of 10, 30.0%), in UH (26 of 29, 89.7%) was higher than in FH (8 of 23, 34.8%), respectively, and statistical significance was remarkable both P < .01). Similar results were obtained for uPAR. The positive rate of uPAR in the high-risk group (22 of 25, 88.0%) was substantially higher compared with that in intermediate-risk group (6 of 17, 35.3%) and low-risk group (2 of 10, 20.0%; P < .01). The positive rate of uPAR in UH (24 of 29, 82.8%) was higher compared with that in FH (6 of 23, 26.1%), and statistical significance was remarkable (P < .01). PGP9.5 mRNA in peripheral blood and BM was detected in 24 of 52 (45.2%) patients. The positive rate of PGP 9.5 mRNA in peripheral blood and BM in the cases positive for uPA (22 of 34, 64.7%) was markedly higher than that in the cases negative for uPA (11.1%, 2 of 18), and statistical significance was remarkable (P < .01). There was significant difference in the positive rate of PGP9.5 mRNA between the group positive for uPAR (66.7%, 20 of 30) and the group negative for uPAR (18.2%, 4 of 22), and a larger difference was found between the group positive for both uPA and uPAR (73.1%, 19 of 26) and the group negative for uPA or uPAR (19.2%, 5 of 26). The overall survival (OS) and event-free survival (EFS) rates at 5 years for all patients were, respectively, 70% +/- 3% and 63% +/- 3% with a median follow-up of 65 months (range 13 to 20). Among all the biologic and clinical features analyzed, multivariate analysis using Cox proportional hazards regression showed that age, MYCN, and combined uPA and uPAR remained significant predictors for both OS and EFS (P < .01, respectively). Both EFS rate and OS rate were significantly better for patients who positively expressed uPA and uPAR than those who negatively expressed uPA or uPAR. CONCLUSIONS: This study showed that uPA and uPAR were overexpressed in high-risk and UH tumor of NB, and that overexpression of both factors was associated with the ability of invasion, metastasis, and prognosis of NB. The presence of high levels of combined uPA and uPAR may be a new prognostic marker that would allow us to identify patients with poorer prognosis who might benefit from more aggressive surgical and adjuvant treatment.

Biomarkers, Tumor↗
PubMed2004

Impact of myocardial contrast echocardiography on vascular permeability: comparison of three different contrast agents.

Microvascular permeabilization, petechial hemorrhage and premature ventricular contractions (PVCs) have been demonstrated in an in vivo rat model of myocardial contrast echocardiography (MCE). The purpose of this study was to compare these effects for three US Food and Drug Administration (FDA)-approved ultrasound (US) contrast agents (US CA): Optison, Definity and Imagent. Evans blue dye, an indicator of microvascular permeability, and a contrast agent were injected IV in anesthetized rats suspended in a water bath to mimic scanning depths seen in clinical echocardiology. Diagnostic US B-mode scans with 1:4 end-systolic triggering were performed at 1.7 MHz using a cardiac phased-array scanhead to provide a short axis view of the left ventricle. To elicit readily measurable effects for comparisons, relatively high doses of the agent were used (50 to 500 microL kg(-1) for Optison, 25 to 200 microL kg(-1) for Imagent, 10 to 100 microL kg(-1) for Definity). Microvascular leakage was characterized by the area of Evans blue dye coloration on the hearts and by extraction of the dye from tissue samples. The number of petechia were counted on the epicardial surface of excised hearts. PVCs were counted from ECG traces recorded with the MCE images. Neither evidence of capillary leakage nor PVCs were seen in sham animals. Based on volume dose, Definity MCE produced more microvascular leakage, but there was no apparent difference between the three agents' microvascular damage potential, which increased linearly with dose at low doses, when expressed in terms of the number of stabilized microbubbles. Definity MCE resulted in fewer PVCs than the other agents. The effects increased strongly with peak rarefactional pressure amplitude, with apparent thresholds for petechiae at 0.4 MPa and for PVCs at about 1.0 MPa. These results should be of value for minimizing adverse potential in diagnosis and optimizing efficacy in therapeutic applications.

Albumins↗
PubMed2004

The effect of time and of vasoactive drugs on capillary leakage induced during myocardial contrast echocardiography.

BACKGROUND: Premature ventricular contractions (PVC), capillary leakage, and petechial hemorrhage can occur during myocardial contrast echocardiography (MCE). The effects occur as a result of the interaction of contrast agent microbubbles and the ultrasound, but the detailed etiology of the effects is not yet clear. This study tested the hypothesis that the capillary leakage results from a physiological response to injury, which might be protracted and modulated by vasoactive drugs. METHODS: Hairless rats were anesthetized and transthoracically scanned with a diagnostic ultrasound system (GE Vingmed System V) at 1.7 MHz with 1:4 triggered frames at end systole. The scan head and rats were mounted in a 37 degrees C water bath to assure free-field conditions and placement of the heart at a similar focal distance as humans. A tail vein was cannulated for injections of Optison contrast agent, vasoactive medications, and Evans Blue dye (EB). EB was injected as a marker of capillary leakage before or after scanning. RESULTS: PVCs, petechia, and capillary leakage occurred during ultrasound exposure of microbubbles in myocardium, with no effects detected in shams. The influence of the vasoactive medications propranolol and isoproterenol on the effects did not support the hypothesis. Capillary leakage occurred during and postexposure, but diminished for EB injection 20 minutes after scanning with or without isoproterenol pretreatment. CONCLUSION: MCE induced PVCs, petechia, and capillary leakage, all of which ended immediately or within 20 minutes after the examination. Contrary to the hypothesis of a physiological mechanism, the capillary leakage appears to be primarily a mechanical effect rather than a physiological response.

Animals↗
PubMed2004

In vivo transfection of NF-kappaB decoy oligodeoxynucleotides attenuate renal ischemia/reperfusion injury in rats.

BACKGROUND: Ischemic acute renal failure (ARF) is a common and often fatal condition characterized by tubular epithelial cell necrosis and marked monocyte infiltration. Inflammatory mechanisms, including cell adhesion, cell infiltration, and cytokine production, are involved. These processes are thought to be directly or indirectly regulated by nuclear factor kappaB (NF-kappaB). Targeted of NF-kappaB might ameliorate ischemia/reperfusion (I/R) injury by inhibiting the production of genes that involved in ischemic ARF. The objective of the present study was to evaluate the effect of NF-kappaB decoy oligodeoxynucleotides (ODN) in experimental rat ischemic ARF. METHODS: Ischemic ARF was induced by left renal artery clamping for 60 minutes, while the right kidney was being removed in female Sprague-Dawley rats. The effect of cationic liposome-protamine-NF-kappaB decoy ODN was evaluated after infusion into the kidney via the renal artery before clamping. After 24 hours of reperfusion, we then assessed morphologic and functional parameters, NF-kappaB/DNA binding activity, monocyte/macrophage (M/MPhi) infiltration, and gene expression in I/R kidney. RESULTS: After 24 hours of reperfusion, compared with sham-operated animals, serum creatinine and blood urea nitrogen (BUN) levels in ischemic ARF animals were increased about 10-fold and fivefold respectively. (255.67 +/- 34.48 micromol/L vs. 25.33 +/- 2.23 micromol/L and 43.47 +/- 5.50 mmol/L vs. 8.45 +/- 0.43 mmol/L, P < 0.001), NF-kappaB/DNA binding activity was markedly elevated [median value was 1.75 vs. 0.15 relative density unit (RDU), P < 0.005]. NF-kappaB decoy ODN treatment reduced the elevation of serum creatinine level by 70% (79.17 +/- 8.64 micromol/L vs. 255.67 +/- 34.48 micromol/L, P < 0.01), BUN level by 40% (28.33 +/- 4.86 mmol/L vs. 43.47 +/- 5.50 mmol/L, P= NS), and almost abolished the NF-kappaB activation compared with levels observed in sham-operated rats (median value was 0.25 vs. 1.9 RDU, P < 0.005). Furthermore, NF-kappaB decoy ODN pretreatment prevented the occurrence of tubular necrosis and reduced the renal tubular damage scores markedly (1.85 +/- 0.06 vs. 3.63 +/- 0.06 scores, P < 0.01). In addition, M/MPhi infiltration was obviously suppressed (9.77 +/- 1.19 cells/hpf vs. 29.22 +/- 1.94 cells/hpf, P < 0.01), Moreover, results of reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry showed the up-regulation of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) was greatly decreased, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expression were also reduced, approaching levels observed in sham-operated animals. The data suggest that NF-kappaB decoy ODN treatment protects renal tissue from the effects of I/R injury and thus reduces the severity of ARF. CONCLUSION: These experiments demonstrated that NF-kappaB plays a critical role in renal I/R injury by reducing a series of inflammatory genes. NF-kappaB decoy ODN treatment reduces the renal dysfunction and damage associated with ischemic ARF. Therefore, in vivo transfection of NF-kappaB decoy ODN provides a new therapeutic strategy for ischemic ARF.

Acute Kidney Injury↗
PubMed2004

Ring finger protein ZIN interacts with human immunodeficiency virus type 1 Vif.

Virion infectivity factor (Vif) protein of human immunodeficiency virus type 1 (HIV-1) is essential for the productive infection of primary human CD4 T lymphocytes and macrophages. Vif overcomes the HIV-inhibitory effects of cellular factor APOBEC3G, which has cytidine deaminase activity. We previously reported the isolation of a Vif-interacting ring finger protein, Triad 3, from a human leukocyte cDNA library, using the yeast two-hybrid system. The full-length cellular protein homologue of Triad 3 has been recently identified as the zinc finger protein inhibiting NF-kappaB (ZIN). Sequence analysis indicates that Triad 3 protein contains all four major ring-like motifs of ZIN. We report here that ZIN binds to purified Vif in vitro and that Triad 3/ZIN interacts with HIV-1 Vif in transfected human 293T cells, as demonstrated by coimmunoprecipitation. To test the biological relevance of this interaction, we produced infectious HIV-1 NL4.3 in the presence or absence of cotransfected ZIN. HIV-1 NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were twofold less infectious in a single-cycle infectivity assay than virus produced in the absence of exogenous ZIN. It was further shown that cells infected with HIV NL4.3 virus stocks produced in the presence of exogenously expressed ZIN were impaired in viral DNA synthesis by twofold. The impairment in viral reverse transcription and the reduction in single-cycle viral infectivity were both shown to be dependent on the presence of Vif in the virus producer cells. The possible mechanisms by which ZIN interferes with the early events of HIV-1 replication are discussed.

Amino Acid Sequence↗
PubMed2004

The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A activity.

The intestinal bacterial metabolites of ginsenosides are responsible for the main pharmacological activities of ginseng. The purpose of this study was to find whether these metabolites influence hepatic metabolic enzymes and to predict the potential for ginseng-prescription drug interactions. Utilizing the probe reaction of CYP3A activity, testosterone 6beta-hydroxylation, the effects of derivatives of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol families on CYP3A activity in rat liver microsomes were assayed. Our results showed that ginsenosides from the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol family including Rb1, Rb2, Rc, Compound-K, Re, and Rg1 had no inhibitory effect, whereas Rg2, 20(S)-panaxatriol and 20(S)-protopanaxatriol exhibited competitive inhibitory activity against CYP3A activity in these microsomes with the inhibition constants (Ki) of 86.4+/-0.8 microM, 1.7+/-0.1 microM, and 3.2+/-0.2 microM, respectively. This finding demonstrates that differences in their chemical structure might influence the effects of ginsenosides on CYP3A activity and that ginseng-derived products might have potential for significant ginseng-drug interactions.

Animals↗
PubMed2004

Gene expression analysis of peroxisome proliferators- and phenytoin-induced hepatotoxicity using cDNA microarray.

The recent DNA microarray technology enables us to understand a large number of gene expression profiling. The technology has potential possibility to comprehend mechanism of multiple genes were related to compounds which have toxicity in biological system. So, the toxicogenomics through this technology may be very powerful for understanding the effect of unknown toxic mechanisms in biological system. We have studied that the effect of compounds related to hepatotoxin in vivo system using DNA microarray and classified chemicals which have been well characterized. We have studied three compounds; 2 peroxisome proliferators: Clofibrate (ethyl-p-chlorophenoxyisobutyrate), gemfibrozil (5-2[2,5-dimethyl-phenoxy]2-2-dimethyl-pentanonic), and an antiepileptic drug: phenytoin (5,5-diphenylhydantoin). Male Sprague-Dawely VAF(+) albino rats of 5-6 weeks old were treated with each compound for 24 hr and 2 weeks. 4.8 K cDNA microarray in house has been used for gene expression profiling. We found that the clustering of gene expression had similarity like as the toxic phenotype of compounds.

Animals↗
PubMed2004

[Relationship of matrilysin with invasion, metastasis, and prognosis in laryngeal cancer].

BACKGROUND & OBJECTIVE: Matrilysin (matrix metalloproteinases-7, MMP-7) might play an important role in invasion and metastasis of tumor and is thought to be related to prognosis of many kinds of carcinomas. This study was designed to investigate the significance of MMP-7 expression in the invasion and metastasis of laryngeal cancer and the relationship of MMP-7 expression with the prognosis of laryngeal cancer. METHODS: The expression of MMP-7 in 70 samples with paraffin-embedded laryngeal cancer and corresponding para-tumor normal mucosas were using immunohistochemical technique. The mRNA expression of MMP-7 were examined by reverse transcription-polymerase chain reaction (RT-PCR) in 24 frozen specimens of laryngeal cancer and corresponding para-tumor normal mucosas. RESULTS: (1) The immunohistochemical staining of MMP-7 was observed in 77.1% (54/70) of cancer tissues, which was significantly higher than that (5.7%, 4/70) of para-tumor normal mucosas (P< 0.01). The mRNA expression of MMP-7 was detected in 75.0% (18/24) of cancer tissues, which was also significantly higher than that (4.2%, 1/24) of para-tumor normal mucosas (P< 0.01). (2) The expression of MMP-7 in protein level was hot only higher in T3-T4 group than that in T1-T2 group (P< 0.01) but also higher in nodal metastases group than that in group without nodal metastases (P< 0.01). (3) The mRNA expression of MMP-7 was significantly higher in T3-T4 group than that in T1-T2 group (2.908 +/- 0.891 vs.1.662 +/- 0.508, P< 0.01) and was significantly higher in nodal metastases group than that in group without nodal metastases (2.958 +/- 0.827 vs. 1.887 +/- 0.769,P< 0.01). (4) Kaplan-Meier survival curve showed that the prognosis of group with MMP-7 protein high expression was poorer than that in group of MMP-7 protein weak or negative expression (log-rank=4.7559, 8.9513; P=0.0292, 0.0028). No significant difference was found between group with MMP-7 protein weak expression and group with that negative expression (log-rank=0.0314, P= 0.8593). CONCLUSION: MMP-7 possesses close relationship with the invasion, metastasis, and prognosis of laryngeal cancer, and it may be served as a marker in estimating the invasive and metastatic potency and prognosis of laryngeal cancer.

Adult↗
PubMed2004

[Potential effect of tumor necrosis factor-alpha and its receptor II gene polymorphisms on the pathogenesis of coal worker's pneumoconiosis].

OBJECTIVE: To approach the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor receptor II (TNFRII) gene polymorphisms on genetic susceptibility of coal worker's pneumoconiosis and their relationship with pulmonary fibrosis. METHODS: Two hundred and thirty-four cases of coal worker's pneumoconiosis (CWP) and four hundred and forty coal mine workers (controls) were selected, and the cases of CWP were divided into three subgroups based on the various stages of I, II and III. 3 ml peripheral vein blood was drawn from every subject. Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha and TNFRII gene polymorphisms were analyzed. RESULTS: In both group matching and 1:1 paired matching, there was no significant difference between CWP workers and controls in distribution frequencies of G/A + A/A (TNF-alpha -308) and T/G + G/G (TNFRII 196) genotypes. The distribution frequency of G/A + A/A genotype in CWP with stage III (20.00%) was higher than those in control (10.91%), and CWP cases with stage I (10.34%) and II (7.50%) respectively. The risk of CWP with stage III in those with G/A + A/A genotype was 2-fold higher than with G/G genotype (OR = 3.00, 95% CI: 0.35 approximately 25.84) for 1:1 paired matching. CONCLUSIONS: TNF-alpha and TNFRII gene polymorphisms does not play an important role in susceptibility to CWP of Han race. TNF-alpha gene promoter polymorphisms might be related with the degree of severe pulmonary fibrosis in CWP.

Aged↗
PubMed2004

[Pressurized solvent extraction in quality control of Chinese herb].

Pressurized solvent extraction (PSE) is a new extraction technology which has been developed in recent years and widely used as sample analysis in environmental, food and pharmaceutical fields. Extraction technique is a key technology in quality control of Chinese herb. Conventional extraction techniques have been a bottleneck of blocking the development of quality control of Chinese herb. This article attempts to review the basic principle, methods, apparatus and main characteristics of PSE and its applications to quality control of Chinese herb.

Chemistry Techniques, Analytical↗
PubMed2004

Using BRFSS data to estimate prevalence of obesity and physical activities in Oklahoma.

UNLABELLED: Obesity has risen at an epidemic rate during the past two decades in the United States. OBJECTIVE: this report describes the obesity prevalence and its relations to physical activities in Oklahoma. METHOD: Used data from Behavioral Risk Factor Surveillance System 2001-2003 for analysis. RESULT: In Oklahoma, the prevalence rates of obesity were increasing in the recent decades and reached 23.3%. People with lower income, fewer years in school, being male, and certain minority groups tend to have higher obesity prevalence rate than others. People with obesity tend to report having chronic diseases. Although self-reported moderate physical activity in Oklahoma has already met the Healthy People 2010 Objective, percentage of no leisure-time physical activity was still high. CONCLUSION: Relationship between prevalence of obesity and physical activity is difficult to interpret. Other risk factors of obesity should be considered in further study.

Adolescent↗
PubMed2004

[The effects of aloesin and arbutin on cultured melanocytes in a synergetic method].

OBJECTIVE: To study the effects of aloesin and arbutin on normal cultured human melanocytes in synergetic method. METHODS: Building up the system of cultured human melanocytes. The cultured melanocytes in vitro were treated with the mixture of aloesin and arbutin. The cell viability and tyrosinase activity was measured by MTT assay, utilization of L-Dopa as the substrate respectively; melanin content was measured by image analysis system. Furthermore, the effects of the mixture on melanocytes were compared with that of aloesin and arbutin. RESULTS: The mixture of aloesin and arbutin showed an inhibition on tyrosinase activity of human melanocytes and reduced significantly melanin content. Between the mixture and the single use of aloesin or arbutin, there is significant difference (P < 0.05). On the other hand, the mixture has little influence on melanocytes viability and there is negative significance. CONCLUSION: The mixture of aloesin and arbutin can significantly inhibit the tyrosinase activity and melanogenesis of cultured human melanocytes. It showed the effects of aloesin and arbutin in a synergistic manner. It is worth to give farther study later.

Arbutin↗
PubMed2004

[Analysis on genetic relationship of Sanjiang White pig and 5 other pig breeds by PAPD].

One hundred primers were used to analyze the polymorphism of kinship of Sanjiang White pig and its parents, Landrace and Dongbei Min pig, Yorkshire, French Hybrids (Fh 019 strain), French Yorkshire by RAPD. Amplification results of 15 primers showed obvious polymorphisms, which were analyzed by clustering. The results indicate that the genetic relationship of Sanjiang White Pig, and Landrace, and Dongbei Min pig are respectively closer(d=0.090,,0.175), and that of Sanjiang White pig and Yorkshire (d=0.263), French Yorkshire (d = 0.223), Fh 019 strain (d = 0.580) are respectively further.

Animals↗
PubMed2004

[Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurized solvent extraction and high performance liquid chromatography].

AIM: To establish a simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps by HPLC coupled with pressurized solvent extraction (PSE). METHODS: The extraction was performed by using PSE and the PSE condition was optimized by using orthogonal test, the contents of ergosterol, nucleosides and their bases in Cordyceps were determined by HPLC. RESULTS: The optimized condition of PSE extraction for ergosterol, nucleosides and their bases in Cordyceps was obtained as follow: solvent, methanol; temperature, 160 degrees C; static extraction time, 5 min; pressure, 10 MPa and one extraction cycle and one time. A ZORBAX NH2 column (250 mm x 4.6 mm ID, 5 microm) and a ZORBAX NH2 guard column (12.5 mm x 4.6 mm ID, 5 microm) were used for simultaneous determination of ergosterol, nucleosides and their bases. Solvents that constituted the mobile phase were A (acetonitrile) and B (10 mmol x L(-1) ammonium acetate in water). The elution conditions applied were: 0 -5.0 min, linear gradient 0 --> 15% B; 5.0-25.0 min, linear gradient 15% --> 20% B; 25.0 - 35.0 min, linear gradient 20% --> 40% B; 35.0 - 45.0 min, linear gradient 40% --> 80% B; 45.0 -50.0 min, 80% B isocratic. The flow-rate was 0. 6 mL x min(-1) and the injection volume was 20 microL. The system operated at 25 degrees C. Ergosterol was monitored and quantified at 275 nm, nucleosides and their bases at 254 nm. CONCLUSION: High performance liquid chromatography coupled with pressurized solvent extraction is a rapid and simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps.

Adenosine↗
PubMed2003

Mitochondrial translocation of cofilin is an early step in apoptosis induction.

Increasing evidence suggests that movement of key proteins in or out of mitochondria during apoptosis is essential for the regulation of apoptosis. Here, we report identification of the actin-binding protein cofilin by a proteomic approach, as such a factor translocated from cytosol into mitochondria after induction of apoptosis. We found that after induction of apoptosis, cofilin was translocated to mitochondria before release of cytochrome c. Reduction of cofilin protein levels with small-interfering RNA (siRNA) resulted in inhibition of both cytochrome c release and apoptosis. Only dephosphorylated cofilin was translocated to mitochondria, and the cofilin S3D mutant, which mimicks the phosphorylated form, suppressed mitochondrial translocation and apoptosis. Translocation was achieved through exposure of an amino-terminal mitochondrial targeting signal in combination with carboxy-terminal sequences. When correctly targeted to mitochondria, cofilin induced massive apoptosis. The apoptosis-inducing ability of cofilin, but not its mitochondrial localization, was dependent on the functional actin-binding domain. Thus, domains involved in mitochondrial targeting and actin binding are indispensable for its pro-apoptotic function. Our data suggest that cofilin has an important function during the initiation phase of apoptosis.

Actin Depolymerizing Factors↗
PubMed2003

[Transfection of nuclear factor-kappaB decoy oligodeoxynucleotides prevents ischemic acute renal failure in rats].

OBJECTIVE: To investigate the effect of nuclear factor kappaB (NF-kappaB) decoy oligodeoxynucletides (ODN) on acute ischemic renal failure (iARF). METHODS: The right kidney was resected and the left renal artery was isolated so as to establish the animal model of iARF in 18 SD rats. Then the 18 rats were divided into 3 groups of 6 rats to be infused into the left renal artery with protamine liposome (PL)-wrapped NF-kappaB decoy ODN (NF-kappaB group), scrambled ODN (scrambled group), or nothing (iARF group) and then underwent clamping of the left renal artery for 60 minutes. Another six rats underwent sham operation with infusion of normal saline and without clamping of the renal artery (sham group). Twenty-four hours later, blood was extracted from the inferior vena cava to detect the serum creatinine (Cr) and blood urine nitrogen (BUN). Normal saline was infused into the aorta to lavage the kidney. Then the kidney was taken to undergo histologic examination and examination of NF-kappaB/DNA binding activity, monocyte/macrophage (M/MPhi) infiltration and MCP-1 gene and protein expression. RESULTS: In the rats injected with PL-wrapped NF-kappaB decoy ODN fluorescence was mainly distributed in the glomeruli 2 hours after injection of NF-kappaB decoy ODN, mainly in the renal tubules 12 hours later, and remarkably subsided after 24 hours. In the rats injected with un-wrapped NF-kappaB decoy ODN, no fluorescence was seen at any time point. After 24 h of reperfusion, compared with sham-operated animals, the serum Scr and BUN levels of the iARF group were about 10-times and 5 times those of the sham operation group (256 micromol/L +/- 84 micromol/L vs. 25 micromol/L +/- 5 micromol/L and 43 mmol/L +/- 13 mmol/L vs. 8.45 mmol/L +/- 1.07 mmol/L respectively. both P < 0.001), the NF-kappaB/DNA binding activity was markedly elevated [with the median values 1.75 vs. 0.15 relative density unit (RDU), P < 0.005], the renal tubular damage score was significantly higher (3.63 +/- 0.15 vs. 0.00 +/- 0.00 scores, P < 0.01), M/MPhi infiltration and the expression of MCP-1 gene were also increased. In comparison with the iARF group, the serum Cr level of the NF-kappaB decoy ODN treatment group was significantly lowered by 70% (79 micromol/L +/- 21 micromol/L vs. 256 micromol/L +/- 84 micromol/L, P < 0.01), the renal tubular damage score was markedly lower (1.85 +/- 0.15 vs. 3.63 +/- 0.15 scores, P < 0.01), and the M/MPhi infiltration and MCP-1 gene expression were inhibited. CONCLUSION: NF-kappaB plays a critical role in renal ischemia/reperfusion injury and NF-kappaB decoy ODN reduces the renal dysfunction and injury associated with I/R of the kidney. In vivo transfection of NF-kappaB decoy ODN provides a novel therapeutic strategy for iARF.

Acute Kidney Injury↗