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PMID |
Sentence |
1 |
2554565
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The adeno-associated virus (AAV) rep gene is transcribed from two promoters, p5 and p19, which code for two over-lapping families of rep proteins.
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2 |
2554565
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We describe here an AAV mutant in which the putative AUG initiation codon in the p19 transcripts was altered and which did not express p19-coded rep proteins.
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3 |
2554565
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The adeno-associated virus (AAV) rep gene is transcribed from two promoters, p5 and p19, which code for two over-lapping families of rep proteins.
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4 |
2554565
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We describe here an AAV mutant in which the putative AUG initiation codon in the p19 transcripts was altered and which did not express p19-coded rep proteins.
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5 |
2845666
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Adeno-associated virus (AAV) vectors readily express the gene for geneticin-resistance under control of the AAV p40 promoter when chromosomally integrated at low copy number in mammalian cells.
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6 |
7474090
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Furthermore, our studies of AAV genomes containing mutated RRS- and/or YY1-binding elements suggest that transcription factor YY1 binding to the transcription start site of P5 interferes with Rep68 repression of the P5 promoter.
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7 |
8151765
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Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels.
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8 |
8151765
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We studied here the regulation of mRNA transcribed from the AAV p5 and p19 promoters, using transient expression in human 293 cells followed by Northern (RNA) blot analysis of the mRNA.
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9 |
8151765
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A plasmid (pNTC3) containing the entire AAV genome with an amber mutation in the rep gene accumulated higher levels of p5 and p19 mRNA than a plasmid containing the wild-type AAV genome.
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10 |
8151765
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A deletion analysis of AAV cis sequences revealed that an intact terminal repeat was not required for negative regulation of p5 and p19 transcript levels and that the regulation of p19 mRNA levels by Rep78 did not require the presence of the p5 promoter.
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11 |
8151765
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Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels.
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12 |
8151765
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We studied here the regulation of mRNA transcribed from the AAV p5 and p19 promoters, using transient expression in human 293 cells followed by Northern (RNA) blot analysis of the mRNA.
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13 |
8151765
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A plasmid (pNTC3) containing the entire AAV genome with an amber mutation in the rep gene accumulated higher levels of p5 and p19 mRNA than a plasmid containing the wild-type AAV genome.
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14 |
8151765
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A deletion analysis of AAV cis sequences revealed that an intact terminal repeat was not required for negative regulation of p5 and p19 transcript levels and that the regulation of p19 mRNA levels by Rep78 did not require the presence of the p5 promoter.
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15 |
8151765
|
Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels.
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16 |
8151765
|
We studied here the regulation of mRNA transcribed from the AAV p5 and p19 promoters, using transient expression in human 293 cells followed by Northern (RNA) blot analysis of the mRNA.
|
17 |
8151765
|
A plasmid (pNTC3) containing the entire AAV genome with an amber mutation in the rep gene accumulated higher levels of p5 and p19 mRNA than a plasmid containing the wild-type AAV genome.
|
18 |
8151765
|
A deletion analysis of AAV cis sequences revealed that an intact terminal repeat was not required for negative regulation of p5 and p19 transcript levels and that the regulation of p19 mRNA levels by Rep78 did not require the presence of the p5 promoter.
|
19 |
8151765
|
Analysis of adeno-associated virus (AAV) wild-type and mutant Rep proteins for their abilities to negatively regulate AAV p5 and p19 mRNA levels.
|
20 |
8151765
|
We studied here the regulation of mRNA transcribed from the AAV p5 and p19 promoters, using transient expression in human 293 cells followed by Northern (RNA) blot analysis of the mRNA.
|
21 |
8151765
|
A plasmid (pNTC3) containing the entire AAV genome with an amber mutation in the rep gene accumulated higher levels of p5 and p19 mRNA than a plasmid containing the wild-type AAV genome.
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22 |
8151765
|
A deletion analysis of AAV cis sequences revealed that an intact terminal repeat was not required for negative regulation of p5 and p19 transcript levels and that the regulation of p19 mRNA levels by Rep78 did not require the presence of the p5 promoter.
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23 |
8676507
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We have identified sequences related to the Rep recognition sequence in the AAV P5 promoter in or near the c-sis proto-oncogene and the genes coding for a hepatocyte glucose transporter, alpha-A-crystallin, and carcinoma marker GA733-1.
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24 |
9032395
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The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV p5 promoter, and the preferred AAV integration site in human chromosome 19, called AAVS1.
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25 |
9032395
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We used the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as query sequences and identified 18 new RRSs in or flanking the genes coding for the following: tyrosine kinase activator protein 1 (TKA-1); colony stimulating factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1; basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9 gene product, which is involved in the chromosomal translocation t (9:11)(p22:q23); the betaB subunit of the hormone known as inhibin; interleukin-2 enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment resident protein called p63; a global transcription activator (hSNF2L); the beta-actin repair domain; a retinoic acid-inducible factor, also known as midkine; a breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G1 cyclin-cyclin-dependent kinase complexes; and the hereditary breast and ovarian cancer gene (BRCA1).
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26 |
9032395
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The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV p5 promoter, and the preferred AAV integration site in human chromosome 19, called AAVS1.
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27 |
9032395
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We used the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as query sequences and identified 18 new RRSs in or flanking the genes coding for the following: tyrosine kinase activator protein 1 (TKA-1); colony stimulating factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1; basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9 gene product, which is involved in the chromosomal translocation t (9:11)(p22:q23); the betaB subunit of the hormone known as inhibin; interleukin-2 enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment resident protein called p63; a global transcription activator (hSNF2L); the beta-actin repair domain; a retinoic acid-inducible factor, also known as midkine; a breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G1 cyclin-cyclin-dependent kinase complexes; and the hereditary breast and ovarian cancer gene (BRCA1).
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28 |
9391128
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The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes mellitus.
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29 |
9391128
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In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes.
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30 |
9391128
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These results demonstrate that maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes.
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31 |
9971790
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These proteins bind the hairpin structures formed by the AAV inverted terminal repeat (ITR) origins of replication, make site- and strand-specific endonuclease cuts within the AAV ITRs, and display nucleoside triphosphate-dependent helicase activities.
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32 |
10482574
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In addition, we show that removal of the secondary Rep68/78 binding site, which is found only in the hairpin form of the AAV ITR, causes a three- to eightfold reduction in the ability of the ITR to be used as a substrate for the Rep78 or MBP-Rep68Delta endonuclease activity.
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33 |
11339817
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We show here that mutation of the Rep recognition sequence, within such a DNA segment derived from the AAV ITRs, eliminates the ability of this substrate to be cleaved detectably by Rep78.
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34 |
12055268
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Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the up-regulation of proinflammatory activity that leads to destruction of insulin-producing pancreatic beta cells in type 1 diabetes.
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35 |
12055268
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In this study, we transferred the BCRF-1 gene, an open reading frame in the Epstein-Barr viral genome with remarkable homology to mouse IL-10 (viral IL-10 or vIL-10), by an adeno-associated viral (AAV) vector to NOD mice to attain sustained vIL-10 gene expression.
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36 |
14712302
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Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice.
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37 |
14712302
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To test the ability of AAT to modulate the development of type I diabetes, we performed a series of investigations involving recombinant adeno-associated virus vector (rAAV)-mediated gene delivery of human alpha-1 antitrypsin (hAAT) to nonobese diabetic (NOD) mice.
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38 |
14712302
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Recombinant AAV-expressing hAAT (rAAV2-CB-AT) was administered intramuscularly to 4-week-old female NOD mice (1 x 10(10) i.u.
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39 |
14712302
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This study suggests a potential therapeutic role for AAT in preventing type I diabetes as well as the ability of AAV gene therapy-based approaches to ameliorate disease effectively.
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40 |
14712302
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Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice.
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41 |
14712302
|
To test the ability of AAT to modulate the development of type I diabetes, we performed a series of investigations involving recombinant adeno-associated virus vector (rAAV)-mediated gene delivery of human alpha-1 antitrypsin (hAAT) to nonobese diabetic (NOD) mice.
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42 |
14712302
|
Recombinant AAV-expressing hAAT (rAAV2-CB-AT) was administered intramuscularly to 4-week-old female NOD mice (1 x 10(10) i.u.
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43 |
14712302
|
This study suggests a potential therapeutic role for AAT in preventing type I diabetes as well as the ability of AAV gene therapy-based approaches to ameliorate disease effectively.
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44 |
15610610
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In HepG2 cells transduced with adeno-associated viral (AAV) vectors encoding LFv2IRE, AP20187 induces LFv2IRE homodimerization and transphosphorylation minutes after drug administration, resulting in the phosphorylation of a canonical substrate of the insulin receptor tyrosine kinase, IRS-1.
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45 |
15621170
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T-cell proliferation and activation markers, CD44 and CD69, were upregulated in NOD donors, suggesting that T-cell activation had occurred prior to pancreas procurement.
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46 |
15621170
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Systemic delivery of a recombinant adenoassociated viral vector (AAV) encoding the viral (vIL-10) IL-10 gene (AAV vIL-10) in NOD recipients protected syngeneic islets from autoimmune destruction.
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47 |
15793254
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To develop primate models of diabetic retinopathy and choroidal neovascularization, rhesus monkeys were injected subretinally or intravitreally with an adeno-associated virus (AAV)-2 vector carrying the cDNA encoding human vascular endothelial growth factor (VEGF).
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48 |
15814672
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Tolerance induction of autoreactive T cells against pancreatic beta cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes.
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49 |
15814672
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In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice.
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50 |
15814672
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This prevention was marked by the inactivation of GAD(500-585)-responsive T lymphocytes, the enhanced GAD(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN-gamma production; especially elevated anti-GAD(500-585) IgG1 titer; and relatively unchanged anti-GAD(500-585) IgG2b titer), the increased secretion of TGF-beta, and the production of protective regulatory cells.
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51 |
15814672
|
These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice.
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52 |
15814672
|
Tolerance induction of autoreactive T cells against pancreatic beta cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes.
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53 |
15814672
|
In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice.
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54 |
15814672
|
This prevention was marked by the inactivation of GAD(500-585)-responsive T lymphocytes, the enhanced GAD(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN-gamma production; especially elevated anti-GAD(500-585) IgG1 titer; and relatively unchanged anti-GAD(500-585) IgG2b titer), the increased secretion of TGF-beta, and the production of protective regulatory cells.
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55 |
15814672
|
These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice.
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56 |
16043104
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We evaluated the effectiveness of a systemically delivered adeno-associated viral vector (AAV vIL-10) carrying viral IL-10 in protecting islet engraftment.
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57 |
16415870
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To induce a sustained impairment in hypothalamic nutrient sensing, adeno-associated viruses (AAV) expressing malonyl-coenzyme A decarboxylase (MCD; an enzyme involved in the degradation of malonyl coenzyme A) were injected bilaterally into the mediobasal hypothalamus of rats.
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58 |
17326253
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In this experiment, human mesenchymal stem cells were transduced with AAV which is containing furin-cleavable human preproinsulin gene to generate insulin-producing cells as surrogate beta-cells for the type 1 diabetes therapy.
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59 |
17328681
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AP20187-mediated activation of a chimeric insulin receptor results in insulin-like actions in skeletal muscle and liver of diabetic mice.
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60 |
17328681
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Systemic AP20187 administration results in time-dependent LFv2IRE tyrosine phosphorylation and activation of the insulin signaling pathway in both liver and muscle of AAV-treated NOD mice.
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61 |
17626070
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To obtain further information that might help to elucidate the mechanism and preferred substrate configurations of preferential integration, we amplified junctions between AAV2 DNA and AAVS1 from AAV2-infected HeLaJW cells and cells with defective Artemis or xeroderma pigmentosum group A genes.
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62 |
18253862
|
This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells.
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63 |
18253862
|
Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein.
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64 |
18253862
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Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19).
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65 |
18253862
|
Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function.
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66 |
18253862
|
This study was conducted to evaluate whether pdx-1 gene delivered by adeno-associated virus (AAV) could induce autologous liver cells to differentiate into insulin-producing cells and to explore the origin of these cells.
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67 |
18253862
|
Here we used 4 x 10e(11) AAV to deliver pdx-1 to STZ-induced diabetic rats via the portal vein.
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68 |
18253862
|
Immunofluorescent staining showed more insulin-positive cells, which had similar morphology with hepatic oval stem cells and were positive for hepatic oval stem cell markers, Thy-1 and cytokeratin 19 (ck19).
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69 |
18253862
|
Our data indicated that rat hepatic oval stem cells were differentiated into bioactive insulin-producing cells by AAV-pdx-1 delivery in diabetic rats, with promoted expression of some transcription factors necessary for beta cell development and function.
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70 |
18545223
|
Systemic Insulin-like growth factor-1 reverses hypoalgesia and improves mobility in a mouse model of diabetic peripheral neuropathy.
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71 |
18545223
|
Peripheral neuropathy is a particularly debilitating complication of both type 1 and type 2 diabetes characterized by sensory and motor neuron damage and decreased circulating levels of insulin-like growth factor 1 (IGF-1).
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72 |
18545223
|
Increased circulating levels of IGF-1 were achieved by delivering a plasmid or adeno-associated viral (AAV) vector bearing mouse IGF-1 to the liver.
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73 |
18545223
|
This latter effect could be seen by merely restoring IGF-1 serum levels to normalcy, which was possible to achieve by IGF-1 gene therapy or insulin treatment.
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74 |
19129396
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We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity.
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75 |
19129396
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Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
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76 |
19129396
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Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation.
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77 |
19129396
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DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin.
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78 |
19129396
|
Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.
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79 |
19129396
|
We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity.
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80 |
19129396
|
Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
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81 |
19129396
|
Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation.
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82 |
19129396
|
DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin.
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83 |
19129396
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Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.
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84 |
20720576
|
In this study, we describe the construction and analysis of a GLP-1 plasmid and double-stranded, adeno-associated viral (dsAAV) expression vector to overcome both the rapid degradation of native GLP-1 and limitations of gene therapy using standard single-stranded AAV.
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85 |
20720576
|
Our study results demonstrate that fasting blood glucose levels of db/db obese mice decreased significantly up to 4 months after a single injection of dsAAV GLP-1, and both insulin and circulating GLP-1 levels increased in dsAAV GLP-1-infected mice.
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86 |
22911805
|
Adeno-associated viral (AAV) vectors of serotype 2 coding for antiangiogenic Pigment Epithelium Derived Factor (PEDF) were injected in the vitreous of a 1.5 month-old transgenic model of retinopathy that develops progressive neovascularization.
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87 |
22911805
|
Normalization of VEGF was consistent with a downregulation of downstream effectors of angiogenesis, such as the activity of Matrix Metalloproteinases (MMP) 2 and 9 and the content of Connective Tissue Growth Factor (CTGF).
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88 |
22911805
|
These results demonstrate long-term efficacy of AAV-mediated PEDF overexpression in counteracting retinal neovascularization in a relevant animal model, and provides evidence towards the use of this strategy to treat angiogenesis in DR and other chronic proliferative retinal disorders.
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89 |
22911805
|
Adeno-associated viral (AAV) vectors of serotype 2 coding for antiangiogenic Pigment Epithelium Derived Factor (PEDF) were injected in the vitreous of a 1.5 month-old transgenic model of retinopathy that develops progressive neovascularization.
|
90 |
22911805
|
Normalization of VEGF was consistent with a downregulation of downstream effectors of angiogenesis, such as the activity of Matrix Metalloproteinases (MMP) 2 and 9 and the content of Connective Tissue Growth Factor (CTGF).
|
91 |
22911805
|
These results demonstrate long-term efficacy of AAV-mediated PEDF overexpression in counteracting retinal neovascularization in a relevant animal model, and provides evidence towards the use of this strategy to treat angiogenesis in DR and other chronic proliferative retinal disorders.
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92 |
23180035
|
In Japanese AAV, significant association was detected with HLA-DRB1*09:01, the carrier frequency of which was increased in MPA [P=0.0087, odds ratio (OR) 1.90, 95% confidence interval (CI) 1.17-3.08] and in myeloperoxidase (MPO)-ANCA-positive AAV (P=0.0016, OR 2.05, 95% CI 1.31-3.23) when compared with healthy Japanese controls.
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93 |
23557700
|
For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats.
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94 |
23557700
|
Next, weanling rats were injected in the VMH with CD36 AAV shRNA.
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95 |
23557700
|
However, VMH CD36-depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance.
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96 |
23557700
|
For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats.
|
97 |
23557700
|
Next, weanling rats were injected in the VMH with CD36 AAV shRNA.
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98 |
23557700
|
However, VMH CD36-depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance.
|
99 |
23577057
|
For this purpose, we used AAV-mediated RNAi knockdown of Atp6i/TIRC7 gene expression to target bone resorption and gingival inflammation simultaneously.
|
100 |
23577057
|
Furthermore, local injection of AAV-shRNA-Atp6i/TIRC7 into the periodontal tissues in vivo protected mice from P. gingivalis infection-stimulated bone resorption by >85% and decreased the T-cell number in periodontal tissues.
|
101 |
23577057
|
Notably, AAV-mediated Atp6i/TIRC7 knockdown also reduced the expression of osteoclast marker genes and inflammation-induced cytokine genes.
|
102 |
23577057
|
This suggests that AAV-shRNA-Atp6i/TIRC7 therapeutic treatment may significantly improve the health of millions who suffer from P. gingivalis-mediated periodontal disease.
|
103 |
23577057
|
For this purpose, we used AAV-mediated RNAi knockdown of Atp6i/TIRC7 gene expression to target bone resorption and gingival inflammation simultaneously.
|
104 |
23577057
|
Furthermore, local injection of AAV-shRNA-Atp6i/TIRC7 into the periodontal tissues in vivo protected mice from P. gingivalis infection-stimulated bone resorption by >85% and decreased the T-cell number in periodontal tissues.
|
105 |
23577057
|
Notably, AAV-mediated Atp6i/TIRC7 knockdown also reduced the expression of osteoclast marker genes and inflammation-induced cytokine genes.
|
106 |
23577057
|
This suggests that AAV-shRNA-Atp6i/TIRC7 therapeutic treatment may significantly improve the health of millions who suffer from P. gingivalis-mediated periodontal disease.
|
107 |
23577057
|
For this purpose, we used AAV-mediated RNAi knockdown of Atp6i/TIRC7 gene expression to target bone resorption and gingival inflammation simultaneously.
|
108 |
23577057
|
Furthermore, local injection of AAV-shRNA-Atp6i/TIRC7 into the periodontal tissues in vivo protected mice from P. gingivalis infection-stimulated bone resorption by >85% and decreased the T-cell number in periodontal tissues.
|
109 |
23577057
|
Notably, AAV-mediated Atp6i/TIRC7 knockdown also reduced the expression of osteoclast marker genes and inflammation-induced cytokine genes.
|
110 |
23577057
|
This suggests that AAV-shRNA-Atp6i/TIRC7 therapeutic treatment may significantly improve the health of millions who suffer from P. gingivalis-mediated periodontal disease.
|
111 |
23577057
|
For this purpose, we used AAV-mediated RNAi knockdown of Atp6i/TIRC7 gene expression to target bone resorption and gingival inflammation simultaneously.
|
112 |
23577057
|
Furthermore, local injection of AAV-shRNA-Atp6i/TIRC7 into the periodontal tissues in vivo protected mice from P. gingivalis infection-stimulated bone resorption by >85% and decreased the T-cell number in periodontal tissues.
|
113 |
23577057
|
Notably, AAV-mediated Atp6i/TIRC7 knockdown also reduced the expression of osteoclast marker genes and inflammation-induced cytokine genes.
|
114 |
23577057
|
This suggests that AAV-shRNA-Atp6i/TIRC7 therapeutic treatment may significantly improve the health of millions who suffer from P. gingivalis-mediated periodontal disease.
|
115 |
23828045
|
At 1 week after multiple low-dose STZ administrations, pancreatic β-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1.
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116 |
23828045
|
This was accompanied by significant upregulation of p53-responsive genes in islets, including a mediator of cell cycle arrest, p21 (also known as Waf1 and Cip1).
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117 |
23828045
|
STZ treatment also suppressed expression of a wide range of genes linked with key β-cell functions or diabetes development, such as G6pc2, Slc2a2 (Glut2), Slc30a8, Neurod1, Ucn3, Gad1, Isl1, Foxa2, Vdr, Pdx1, Fkbp1b and Abcc8, suggesting global β-cell defects in STZ-treated islets.
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118 |
23828045
|
When a pancreas-targeted adeno-associated virus (AAV) vector was employed for long-term Glp-1 gene delivery, pancreatic GLP-1 expression protected mice from STZ-induced diabetes through preservation of the β-cell mass.
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119 |
23828045
|
Upon pancreatic GLP-1 expression, upregulation of Cxcl13 and Nptx2 was observed in STZ-damaged islets, but not in untreated normal islets.
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120 |
23828045
|
Given the pro-β-cell-survival effects of Cxcl12 (Sdf-1) in inducing GLP-1 production in α-cells, pancreatic GLP-1-mediated Cxcl13 induction might also play a crucial role in maintaining the integrity of β-cells in damaged islets.
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