Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing resistance to currently used antimicrobials has resulted in the evaluation of other agents that have antimicrobial activity against Helicobacter pylori. H. pylori American Type Culture Collection (ATCC) strain 49503 (a toxin-producing strain known to be associated with gastric cancer) was grown, a cell suspension prepared in 2 mL PBS and diluted 10-fold. One hundred microL of this cell suspension was added to vitamin C 0.5%, vitamin E 0.5%, garcinol 100 microg/mL, Protykin (containing 50% trans-resveratrol) 100 microg/mL and garcinol + Protykin 100 microg/mL in Lennox broth, and incubated for 16 h under microaerophilic conditions. Three replicates of 10 microL from each 10(-7) dilution tube were plated, colonies were counted after 16 h, and growth of H. pylori was confirmed by the CLO test. These colony counts were compared to control cultures without the addition of any antioxidants. The experiments were then repeated with the addition of 15 microg/mL of clarithromycin to experimental and control samples. Enhanced killing of H. pylori by 37.6% was noted when vitamin C was added, which increased to 66% when clarithromycin was added, compared to controls (p < 0.05). With garcinol and Protykin alone there was 91.4 and 87% killing of H. pylori, respectively, while a combination of garcinol + Protykin resulted in 90.8% killing compared to controls (p < 0.05). When clarithromycin was added, there was 76.3% increased killing with garcinol alone, 55.3% with Protykin alone, and 73.7% with garcinol + Protykin compared to controls (containing clarithromycin) (p < 0.05). Vitamin E had no effect on H. pylori growth compared to controls. We conclude from this study that some antioxidants such as vitamin C, garcinol and Protykin, but not vitamin E, may have potential as antimicrobial agents against H. pylori.
Mol Cell Biochem 2005 Feb
PMID:Antimicrobial effects of antioxidants with and without clarithromycin on Helicobacter pylori. 1579 61

Previous studies mainly evaluated the effect of culture conditions on preimplantation embryo apoptosis. In order to inhibit apoptosis of nuclear transfer (NT) embryos, putative apoptosis inhibitors were used to treat donor cells. However, little is known about the effect of activation treatments on embryo apoptosis. We firstly investigated the effect of various parthenogenetic activation (PA) treatments on embryo development, blastocyst cell number, and apoptosis, and then one of these activation treatments proved to be most efficient was selected for activation rabbit NT embryos. The activation by electrical pulses and 30 min later, electroporation with 25 muM D-myoinositol 1,4,5-trisphosphate (IP3) in Ca(2+)- and Mg(2+)-free PBS, then exposure to 2.0 mM 6-dimethylaminopurine (6-DMAP) for 3 hr effectively activated rabbit oocytes, and resulted in significantly a higher blastocyst development rate (72.7%) and total cell number (175 +/- 14.1), and markedly lower apoptosis level of blastocyst (4.3 +/- 0.5) than all the other groups. When the same activation protocol was applied in NT embryo activation, we found that exposure of the embryos to 6-DMAP for 3 hr could decrease the apoptosis level of blastocyst and increase blastocyst rate and cell number. The results demonstrate that oocyte activation affects not only embryo development and quality but also embryo apoptosis.
Mol Reprod Dev 2005 Sep
PMID:Parthenogenetic and nuclear transfer rabbit embryo development and apoptosis after activation treatments. 1595 17

To test the hypothesis that overexpression of early growth response factor-1 (Egr-1) contributes to the revascularization of ischemic limbs, a constitutively active form of Egr-1 (Egr-1*) was made and evaluated in vitro and in vivo. Analyses of the transduced myocytes revealed significant upregulation of bFGF, PDGF-A, PDGF-B, IGF-II, and TGF-beta1. A coculture assay of the paracrine effects indicated that Ad-Egr-1* promoted proliferation and migration of endothelial cells. When Ad-Egr-1* was injected into the tibialis anterior muscle of mice, followed by explant culture in growth factor-reduced Matrigel, many capillary-like structures were observed in the Egr-1* group compared with minimal sprouting from the LacZ group, suggesting an angiogenic potential of Egr-1*. Next we evaluated Ad-Egr-1* in a murine model of hindlimb ischemia. Compared with slow revascularization in the control PBS or LacZ group, a rapid increase in tissue perfusion was observed in the Egr-1* group and the difference in flux ratio was statistically significant at day 7. In the injected muscle, expression of Egr-1*, upregulation of its target genes, and increased number of vessels staining positive for smooth muscle alpha-actin were observed. These results suggest that Egr-1 plays an important role in vascular recovery after occlusion and could be a potential target for therapeutic angiogenesis.
Mol Ther 2005 Aug
PMID:Adenoviral-mediated delivery of early growth response factor-1 gene increases tissue perfusion in a murine model of hindlimb ischemia. 1604 1

To improve bystander cell killing with HSV-TK/GCV, we have utilized dFdCyd to reduce endogenous dGTP, which competes with GCVTP for incorporation into DNA. In this study we demonstrate the ability of dFdCyd to enhance GCV-mediated bystander cytotoxicity in cultured SW620 human colon carcinoma cells as well as in a murine xenograft model. In vitro, dFdCyd reduced cellular dGTP levels and produced a fourfold increase in the GCVTP:dGTP ratio. This elevated GCVTP:dGTP ratio resulted in a twofold increase in GCVMP incorporation into DNA in bystander cells cocultured with HSV-TK-expressing cells. The combination of GCV and dFdCyd was determined to be synergistic by isobologram analysis of bystander cytotoxicity. Tumors in mice treated with GCV and dFdCyd exhibited a significant growth delay requiring 40 days to obtain approximately 10 times their initial size compared to tumors in PBS- or single-drug-treated animals, which grew rapidly, increasing to a similar size in just 19 to 24 days. In addition, complete tumor regression was observed only in animals treated with both drugs. Furthermore, dFdCyd alone or in combination with GCV produced no evidence of toxicity or significant weight loss. These data suggest that dFdCyd may improve the clinical efficacy of HSV-TK/GCV gene therapies.
Mol Ther 2005 Dec
PMID:In vitro and in vivo enhancement of ganciclovir-mediated bystander cytotoxicity with gemcitabine. 1610 24

Increased cAMP improves neuronal survival and axon regeneration in mammals. Here, we assess cAMP levels and identify activated pathways in a spontaneously regenerating central nervous system. Following optic nerve crush in goldfish, almost all retinal ganglion cells (RGC) survive and regenerate retinotectal topography. Goldfish received injections of a cAMP analogue (CPT-cAMP), a protein kinase A (PKA) inhibitor (KT5720), both compounds combined, or PBS (control). RGC survival in experimental groups was unaffected at any stage. The rate of axon regeneration was accelerated by the activator and decelerated both by the inhibitor and by combined injections, suggesting a PKA-dependent pathway. In addition, errors in regenerate retinotectal topography were observed when agents were applied in vivo and RGC response to the guidance cue ephrin-A5 in vitro was altered by the inhibitor. Our results highlight that therapeutic manipulation of cAMP levels to enhance axonal regeneration in mammals must ensure that topography, and consequently function, is not disrupted.
Mol Cell Neurosci 2005 Nov
PMID:cAMP regulates axon outgrowth and guidance during optic nerve regeneration in goldfish. 1616 47

Antibacterial responses have been studied in Atlantic salmon following an acute intra peritoneal injection of a genetically attenuated (aroA(-)) strain of Aeromonas salmonicida known to elicit protective immunity. Three tissues were studied for transcriptional changes, the liver, head kidney and the gill. RNA was collected from fish 6, 12, 24 and 48 h following infection or at the same time points from fish injected with PBS as non-infected control. PCR-select cDNA subtraction libraries were constructed from pooled 24 and 48 h post infection RNA to identify up-regulated mRNAs. One thousand four hundred and eighty six cDNA clones were sequenced from enriched cDNA libraries, of which 71% had significant homologies to known functional proteins. Many of these clones have previously been un-characterised in Atlantic salmon. A salmonid cDNA microarray was used to further analyse the gene expression profile as the library construction in itself does not answer the dynamics of the response. The greatest increase in expression identified in the array analysis was a liver antibacterial peptide, hepcidin that was increased 11-fold following the challenge. A panel of clones were chosen for semiquantitative reverse transcriptase PCR from all time points sampled. These results indicated there were both temporal differences and tissue differences in the transcriptional response to bacterial exposure, potentially of relevance to the establishment of protection.
Mol Immunol 2006 Apr
PMID:Transcriptome response following administration of a live bacterial vaccine in Atlantic salmon (Salmo salar). 1631 60

The aim of this study was to investigate antioxidant, anti-inflammatory, and antibacterial properties of propolis in the treatment of experimental Staphylococcus aureus keratitis. Twenty young New Zealand white rabbits were used in this experiment. Staphylococcus aureus were given by intrastromal injection to 16 rabbits and 4 rabbits were used as control group (Group 1). Group 2 was treated with phosphate-buffered solution drops; Group 3 was administered ethanolic extract of propolis drops; Group 4 received topical ciprofloxacin drops; Group 5 was treated with topical ciprofloxacin drops along with ethanolic extract of propolis drops. The eyes were examined by slit lamp to assess corneal opacity. And then, corneas were removed to determine nitric oxide (NO) levels and count bacteria. Corneas were also evaluated histologically. Corneal NO concentration in group 5, treated with a combination of propolis and ciprofloxacin was determined significantly lower (10.0+/- 1.8 micromol/g wet tissue) than in Group 4, treated with ciprofloxacin (24.0+/- 3.1 micromol/g wet tissue), from Group 3, treated with propolis (15.6+/- 1.8 micromol/g wet tissue), and treated with PBS (44.7+/- 7.8 micromol/g wet tissue). There were significantly fewer bacteria in eyes that received propolis plus ciprofloxacin than in eyes treated with ciprofloxacin (p = 0.0001) or propolis (p = 0.0001) or eyes treated with PBS (p = 0.0001). The light microscopic examination revealed that the control group showed normal corneal morphology. In the nontreated group, sections of the stromal infiltration revealed the presence of inflammatory cells, which were diffusely distributed (p < 0.05). Administrations of ciprofloxacin plus propolis resulted in a significantly reduced histological damage with fewer bacterial inoculation of the corneal stroma in comparison with the other groups (p < 0.05). Based on these findings, we suggest that ethanolic extract of propolis has antioxidant, anti-inflammatory, and antibacterial properties for S. aureus keratitis in rabbits.
Mol Cell Biochem 2006 Jan
PMID:The protective role of topical propolis on experimental keratitis via nitric oxide levels in rabbits. 1632 68

Previous studies have shown that oligodeoxynucleotides containing unmethylated CpG motifs were used as adjuvants for immunoregulation and immune response. This study was to explore the activation effects of Bifidobacteria DNA containing unmethylated CpG motifs (CpG DNA) on murine macrophage J774A.1 cells. The genomic DNA of Bifidobacteria was extracted and purified, and the methylation degree of CpG motifs was tested. The phagocytic ability of the macrophages was detected by flow cytometry. The cytokines (IL-1beta, IL-6, IL-12p40 and TNF-alpha) levels in the culture supernatants of Bifidobacteria DNA treated J774A.1 cells were assayed by ELISA. The content of nitric oxide (NO) was detected by Griess reagent. After treated with Bifidobacteria DNA for 24 h, Nile Red stain increased in J774A.1 macrophage, which suggested that the lipid metabolism increased in the macrophages. The phagocytic ability and levels of NO and cytokines of IL-1beta, IL-6, IL-12p40 and TNF-alpha were significantly higher than PBS group and CT DNA group. The results indicated that Bifidobacteria DNA could activate murine macrophages J774A.1, which could provide scientific basis for the research and application of microorganism DNA preparation.
Cell Mol Immunol 2005 Dec
PMID:Bifidobacteria DNA induces murine macrophages activation in vitro. 1642 99

RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCL5) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-gamma levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-gamma-producing CD4 T cells in lung, and IFN-gamma production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-gamma, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-gamma and IL-12.
Am J Respir Cell Mol Biol 2006 Aug
PMID:RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge. 1684 5

This study investigated whether the therapeutic index of regional melanoma therapy using parenteral temozolomide could be improved by chemomodulation with O6-benzylguanine (O6BG), an inhibitor of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT). Using a nude rat s.c. human melanoma xenograft model of the extremity, tumors were analyzed for AGT level 2 to 3 hours after the i.p. injection of 3.5 to 70.0 mg/kg O6BG to inhibit AGT activity. Survival studies were conducted using animals that were treated with a 15-minute isolated limb infusion with 10% DMSO in PBS (control), temozolomide alone, or temozolomide in conjunction with single or multiple doses of i.p. O6BG. Tumor volume and toxicity level were monitored every other day. Administration of 3.5 mg/kg O6BG depleted tumor AGT activity by 93.5% (P < 0.01). Groups treated with regional temozolomide alone (350 mg/kg), systemic temozolomide with O6BG, or vehicle combined with O6BG showed no significant tumor responses compared with controls. Whereas use of regional temozolomide alone at a higher dose (750 mg/kg) showed some degree of tumor response, regional temozolomide given in conjunction with multiple dosages of O6BG showed a marked (P < 0.01) reduction in tumor growth with minimal toxicity. Our findings suggest that AGT modulation by the administration of O6BG in combination with temozolomide regional chemotherapy leads to a significant improvement in melanoma antitumor responses. Clinical trials using chemotherapy modulation may improve response rates in future regional infusion and perfusion drug trials.
Mol Cancer Ther 2006 Mar
PMID:Modulation of chemotherapy resistance in regional therapy: a novel therapeutic approach to advanced extremity melanoma using intra-arterial temozolomide in combination with systemic O6-benzylguanine. 1654 88


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