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"Therefore, it is most likely that vascular endothelial cells contribute to the increased amount of circulating PAI induced by TNF in vivo."

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"PAI-1 gene and protein expression were induced consistently by TGF-beta (up to 4.0-fold), PDGF (2.1-fold), TNF-alpha (1.7-fold), and thrombin (2.3-fold)."

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"Tumor necrosis factor alpha induced PAI-1 mRNA accumulation with the same magnitude and time course as IL-1, and was not additive with IL-1."

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"In vitro study using HGrC1 shows that TGF-beta and TNF-alpha increase PAI-1 mRNA and its activity, and both together exhibit a synergistic effect."

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"To investigate whether or not hypoxia, TNF-alpha, and their combination actually increase the transcriptional activity of the human PAI-1 promoter, transient transcription assay using pGL3 PAI-1 was c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Both superoxide (generated by xanthine oxidase plus hypoxanthine) and hydrogen peroxide were potent inducers of PAI-1, and hydroxyl radical scavengers completely abolished the TNF-alpha induction of PAI-1."

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"TNF-alpha increased the PAI-1 release in a dose dependent manner, and the maximal levels of PAI-1 (35.3 +/-1.00 ng/ml, a 2.8-fold increase compared with control) were observed at a 3-h incubation with[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"However, TNF-alpha increases PAI-1 biosynthesis at least by increasing ceramide levels, which are not de novo synthesized but are a SM breakdown product."

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"C 2 -dihydroceramide failed to suppress the increase in PAI-1 release induced by staphylococcal SMase, while aspirin was found to selectively suppress the increase in PAI-1 release induced by the SMas[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"LPS, cytokines and growth factors (IL-1, TNF-a) are known to stimulate IL-6 production in several cell types including fibroblasts and endothelial cells [16,32], and in a preliminary study, we found t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"TNF-alpha and IL-1 stimulate PAI-1 synthesis and release , and decrease plasminogen activator synthesis ."
| PMC

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"Because TNF-alpha may impair insulin signalling, inhibit lipoprotein lipase, induce PAI-1, and directly contribute to endothelial dysfunction, this cytokine may be involved in the pathogenesis of preeclampsia [XREF_BIBR]."

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"Time course studies showed that TNF-alpha induced PAI-1 mRNA within 2 hours, and the induction peaked in 4 to 6 hours, but was dramatically attenuated in the presence of 1,25 (OH) 2 D 3 (XREF_FIG)."

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"For this purpose, we observed that when VSMCs were pretreated with parthenolide and therefore NF-kappaB pathway was inhibited, the production of PAI-1 induced by TNF-alpha was partially reduced."

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"These molecules include transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), angiotensin II and interleukin 6 (IL-6), all of which up-regulate PAI-1 in various cell types or can be up-regulated by PAI-1."

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"TNF alone increased PAI-1 accumulation in the culture medium in a time- and dose dependent fashion, but this increase was abolished when A23187 was added simultaneously with TNF."

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"TNFalpha induced PAI-1 mRNA and protein expression, whilst PG and RG, at 10 muM, attenuated TNFalpha mediated induction of PAI-1 mRNA and protein expression (Figs. 1 D-F)."

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"PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway, while TGF-beta is the most important cytokine for PAI-1 transcriptional activation through its 5' proximal promoter."

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"Thus TNF may mediate increased PAI-1 release in inflamed peritoneum."

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"The induction of PAI-1 by TNF-alpha and insulin is mediated, in part, by ERK and p38 MAPK."

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"WA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1."
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"At this stage, we explored whether or not TNF-alpha could be increasing the production of PAI-1 in VSMCs through the activation of NF-kappaB."

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"The current results demonstrate that IL-6 in (pre) adipocyte CM stimulates the production of fibrinogen by HepG2 cells and that IL-1beta and TNF-alpha in (pre) adipocyte CM induce an increase in PAI-1 production by HepG2 cells (XREF_FIG)."

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"We investigated how, during phorbol ester induced differentiation of HL-60 cells, the secreted TNFalpha modulated plasminogen activator inhibitor type I (PAI-1) and gelatinase B (MMP-9) syntheses, two proteins involved in pericellular proteolysis."

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"Tumor necrosis factor alpha activates the human plasminogen activator inhibitor-1 gene through a distal nuclear factor kappaB site."

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"Collectively, these results indicate that TNF-alpha increased the PAI-1 and t-PA ratio, which was inhibited by compounds 1 and 2."

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"It is noticeable that the induction of PAI-1 by TNFalpha was more robust in VDR (-/-) cells (XREF_FIG), consistent with a repressive role of VDR in NF-kappaB regulation."

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"In THLE-5b hepatocytes, TNF-alpha and the local renin-angiotensin system coordinately stimulate PAI-1 production."

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"Studies in which exogenous TNF-alpha was infused into lean mice lacking individual TNFRs indicate that TNF-alpha signaling of PAI-1 in adipose tissue can be mediated by either the p55 or the p75 TNFR."

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"To examine the direct effect of PL on TNF-alpha stimulated PAI-1 secretion, HUVECs were cultured in media with or without PL in the presence and absence of TNF-alpha for 18 h."

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"The PAI-1 promoter is activated by TNF-α via an NFκB 5′ upstream element and directly activated by TGF-β1 via SMAD2/3 promoter binding sites[82,94,95]."

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"Tumor necrosis factor-alpha (TNF-alpha) was found to induce type-1 plasminogen activator inhibitor (PAI-1) antigen in the human fibrosarcoma cell line HT-1080, and PAI-1 and urokinase-type plasminogen activator (u-PA) antigens in the human carcinoma cell line T-CAR1; tissue-type plasminogen activator (t-PA) antigen was not affected or slightly decreased."

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"It also inhibited the FXa and thrombin productions, and also decreased TNF-α–induced PAI-1 production (Lee et al., 2015)."

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"The substances secreted by these cells, known as adipocytokines, include leptin, adiponectin, angiotensinogen, resistin, tumor necrosis factor alpha (TNF-alpha) receptor activating peroxisome proliferation gamma (PPAR-gamma), interleukin-6 (IL-6), insulin like growth factor-1 (IGF-1), lipoprotein lipase (LPL), and adipsin (plasminogen activator inhibitor 1 - PAI-1) [XREF_BIBR, XREF_BIBR]."

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"TNF alpha (0 to 100 ng/ml) had no effect on t-PA synthesis, but enhanced PAI-1 release in a time- and dose dependent manner (97% increase of PAI-1 synthesis after a 24 hour incubation)."

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"WA increased bleeding time and also suppressed TNF-alpha induced PAI-1 synthesis in vivo and ex vivo studies."

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"The increase of these " cardiovascular risk factors " levels will be probably induced by higher activity of inflammatory cytokines IL-1 beta and/or TNF alpha in NIDDM patients, because both are inducers of orosomucoid fibrinogen and PAI-1 synthesis."

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"CTXA prolonged in vivo bleeding time and inhibited TNF-alpha induced PAI-1 production."

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"This could be confirmed for p-selectin; however, TNFalpha dependent induction of PAI-1 and suppression of thrombomodulin seemingly depended predominantly on TNFR1, while both TNFR subtypes were required for the upregulation of tissue factor and endothelial dependent clotting."

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"The present study also found that the main Ashitaba chalcone XA inhibited TNFa induced PAI-1 mRNA increases in EA.hy926 cells (data not shown)."

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"The PAI-1 promoter is activated by TNF-α via an NFκB 5′ upstream element and directly activated by TGF-β1 via SMAD2/3 promoter binding sites[ xref , xref , xref ]."

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"N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes."

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"In contrast to these findings, troglitazone was reported however, to inhibit TNFalpha stimulated PAI-1 secretion from human endothelial cells (Kato et al., 1999; Nordt et al., 2000) as well as from cu[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"The difference in dose of TNF-alpha does not account for the different results, since 100 U/ml of TNF-alpha induced PAI-1 to near the maximal level in our experiments (a 2.5-fold increase, data not sh[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We have shown that TNF-alpha upregulates the production of PAI-1 in a nonmalignant human liver cell line, THLE-5b (Takeshita et al., 2006), as has been reported in human umbilical vein endothelial cel[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Recombinant human tumor necrosis factor-alpha (TNF-alpha) strongly upregulated PAI-1 synthesis in PMA- or TGF-beta1 and D3-differentiated cells, and the potentiating effect of atorvastatin was of the same order as in the absence of TNF-alpha."

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"Systemic inflammatory TNFα and IL1β can upregulate PAI‐1 synthesis, especially in sepsis‐induced systemic inflammation by gram‐negative bacteremia ."

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"In addition, the induction of PAI-1 by TNF-alpha and plasminogen suggests a negative feedback mechanisms limit both plasmin mediated and MMP mediated matrix degradation."

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"Tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) increased in several, but not all, cell lines the production of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and plasminogen activator inhibitor type 1 (PAI-1) as analysed by zymography, enzyme immunoassays and Northern analysis."

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"The co-expressed genesets show SERPINE1 is up-regulated by TNF and corticosteroids, which impairs the fibrinolytic activity and affects vascular angiogenesis and tissue remodeling leading to delayed or impaired wound healing."

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"These results demonstrate that NF-kappaB is likely to mediate the induction of PAI-1 by TNF-alpha or LPS in MEFs, and predict a cis-kappaB element in the pai-1 gene promoter."

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"Although it has been reported that both TNF and LPS lead to PAI-1 release from endothelial cells in vitro, inhibition of TNF did not decrease PAI-1 concentration in SLD and LPS cotreated rats (XREF_FIG)."

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"IL-1 alpha and TNF alpha increased the synthesis of PAI-2 and PAI-1 by EC in a dose dependent manner."

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"TNFalpha (20 U/ml) drastically enhanced PAI-1 accumulation (by a factor of 3.8) in the culture medium and mRNA levels, which is concordant with previous data [33,34]."

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"The results showed that TNF-alpha increased PAI-1 production in both a dose dependent and time dependent manner, and EGCG prevented TNF-alpha-mediated PAI-1 production and reduced phosphorylation of ERK1/2."

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"Administration of TNF-alpha to lean mice significantly increased PAI-1 mRNA in adipose tissue, leading to a pattern similar to that found in obese mice [XREF_BIBR]."

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"We identified a functional cis-kappaB element in the proximal promoter of the mouse pai-1 gene that mediates the up-regulation of PAI-1 by TNFalpha and LPS."

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"Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNFalpha or LPS, and the induction was blocked by 1,25 (OH) 2 D 3."

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"Because TNFalpha induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFalpha."

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"Because TNFalpha induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFalpha."

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"Even this low level of TNF-alpha signaling, if sustained, may be sufficient to stimulate the production of PAI-1 by adipocytes."

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"The data presented above support a mechanism by which TNFalpha (by way of ERK1/2) induces PAI-1; this induction inhibits fibrinolysis, causing fibrin to accumulate (see XREF_FIG)."

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"It is important to note that the GFP tagged construct does not contain an NF-kappaB promoter, which is the general mediator for TNF-alpha induced increases in PAI-1 24."

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"In this study, we identified a functional NF-kappaB binding site within the mouse pai-1 gene promoter and demonstrated that 1,25 (OH) 2 D 3 suppressed the up-regulation of PAI-1 induced by pro inflammatory factors (TNFalpha and LPS) by blocking NF-kappaB activation."

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"Therefore, collectively, these results indicate that the PAI-1 and t-PA ratio was increased by TNF-alpha and that PPG prevented this increase (XREF_FIG C)."

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"For examples, the proinflammatory cytokines IL-6 and TNF-alpha induce leptin and PAI-1 production; in turn, leptin and resistin upregulate secretion of proinflammatory cytokines; and hyperleptinemia, IL-6, and TNF-alpha all contribute to hyperinsulinemia and insulin resistance."

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"These data demonstrate that TNF-alpha rather than IL-6 stimulates an increase in PAI-1 mRNA in the subcutaneous adipose tissue, suggesting that TNF-alpha may be involved in the pathogenesis of related metabolic disorders."

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"Activated macrophages secreted detectable levels of TNF, and administration of exogenous TNF significantly decreased trophoblast invasiveness (P < 0.05), increased the secretion of PAI1 (P < 0.01), and completely inhibited the pro-uPA-associated caseinolytic activity by binding to the TNF receptor 1."

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"In this report, we demonstrate for the first time that the treatment with liraglutide, a long acting GLP-1 analogue, inhibited TNF or hyperglycaemia mediated induction of PAI-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 mRNA and protein expression in a human vascular endothelial cell line."

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"The monokine tumor necrosis factor (human recombinant TNF) increased the production of PAI by cultured human endothelial cells from umbilical vein (twofold) and from foreskin microvessles (four to eight fold)."

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"As expected, TNF induced a strong release of PAI-1, in sharp contrast to its effects on TPA release."

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"A 5′ distal TNFα-responsive enhancer of the PAI-1 gene is located 15 kb upstream of the transcription start site containing a conserved NF-κB-binding site that mediates the response to TNFα."

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"Endotoxin and TNFa stimulate PAI-1 production in the liver, kidney, lung and adrenals of mice."

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"However, in the presence of tat, TNF (1 U/ml) significantly enhanced PAI-1 production."

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"In our experimental model, TNF-α induced PAI-1, shifting the vascular equilibrium toward a more procoagulant state."

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"A reduced p70 S6 kinase (p70 (S6K)) phosphorylation was also observed and, in this situation, TNF dramatically enhanced PAI-1 synthesis."

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"Ohkura et al. reported that xanthoangelol (1), xanthoangelol B (5), and xanthoangelol D (9) isolated from the exudates of A. keiskei suppressed production of TNFa-induced PAI-1, an inhibitor of fibrinolysis, in human umbilical vein endothelial cells (HUVECs) (Ohkura et al. 2011 )."

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"Irradiation, TNF alpha and LPS have already been shown to induce increased endothelial cell PAI-1 production [22-24] which correlates to the already mentioned elevated PAI-1 serum levels in VOD patien[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"PAI-1 gene activation by TNF-alpha apparently is yet to be defined for the location of the response element and/or the signaling pathway, while TGF-beta is the most important cytokine for PAI-1 transcriptional activation through its 5 ' proximal promoter."

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"TNF-alpha modulates statin effects on secretion and expression of MCP-1, PAI-1 and adiponectin in 3T3-L1 differentiated adipocytes."

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"It has been shown that the relationship between diabetes and visceral fat is attenuated by levels of adiponectin, IL-6, TNF-alpha, and plasminogen activator inhibitor 1, indicating the possibility that adipocytokines are key in the link between visceral fat and an unfavorable metabolic profile."

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"PAI-1 is an early response protein and can be induced by different cytokines/chemokines/gro wth factors including transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNFalpha), and angiotensin II."

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"Baicalin also prolonged in vivo bleeding time and inhibited TNF-alpha induced PAI-1 production."

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"In most early infected patients the level is mainly suppressed by increasing production and release of PAI-1 in response to : cytokine TNF-alpha (tissue necrosis factor- alpha) that stimulates PAI-1 release from ECs, and the adipocytes in obese subjects, interference of the renin-angiotensin system (RAAS) with loss of effective ACE2 receptors inflammatory responses that induce platelets and macrophages to release PAI-1 hypoxia that induces monocytes to release PAI-1, reduced levels of APC."

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"Similarly, TNF significantly up-regulated PAI-1 synthesis when p70 (S6K) phosphorylation was inhibited by rapamycin."

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"We demonstrated that TNF alpha in a nanomolar dose range stimulated PAI-1 messenger RNA (mRNA; Northern blots) as well as immunoreactive (Western blots) and bioactive (Stachrom) PAI-1 protein."

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"Induction of PAI-1 by TNF alpha could be related to restricted trophoblast invasion in preeclampsia."

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"PAI-1 mRNA level in the cells treated with TNF-alpha were significantly increased by 3.3-fold at 24 hours, and by 2.2-fold at 48 hours compared with those in the control cells at 24 hours Figure 5a."

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"In contrast, PAI-1 : Ag release was significantly increased by either IL-1 beta or TNF alpha; ET-1 significantly reduced the stimulatory effect of the cytokines."

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"In endothelial cells, LPS and TNFalpha increased PAI-1 mRNA after 6-24h, but no increase in PAI-1 release was observed; ascorbate did not affect these responses."

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"However, as TNFalpha increased t-PA and PAI-1 in smooth muscle cells, it is suggested that other pathways and factors are involved in fibrinolysis modulation."

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"Results obtained suggest that TNF-alpha stimulates PAI-1 production by adipocytes, an effect potentiated by insulin, and that adipocyte generation of reactive oxygen centered radicals mediates the induction of PAI-1 production by TNF-alpha."

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"Additionally, sustained increased levels of proinflammatory cytokines TNF-alpha and IL-1beta can cause increased production of PAI-1 in ECs within the plaque."

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"TNF (100 U/ml) treatment of endothelial cultures induced steady state levels of uPA and PAI-1 mRNA following a 18 hr treatment both 6-fold and 2-fold, respectively utilizing northern analysis."

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"Pleural inflammation caused by TB may enhance the release of proinflammatory cytokines, particularly TNF-alpha, which subsequently may increase PAI-1 and decrease tPA in pleural fluid."

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"Additionally, we found that TNF-alpha promotes the production of PAI-1 mRNA and protein in THLE-5b cells (Takeshita et al., 2006)."

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"PAI-1 is highly stimulated by TNFalpha and LPS [XREF_BIBR], thus NF-kappaB is thought to be a crucial transcriptional regulator for PAI-1."

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"Treatment of BAEC with either IL-1, LPS, or human recombinant tumor necrosis factor and cachectin (TNF) dramatically increased the level of PAI mRNA."

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"Thus, TNF-alpha contributes not only to the elevated expression of PAI-1 in adipose tissue but also to the increased PAI-1 observed in the kidney, heart, liver, and lung of ob/ob mice.To investigate t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"TNF-alpha and IL-1 stimulate PAI-1 synthesis and release, and decrease plasminogen activator synthesis."
| PMC

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"In platelets, thrombin, but not LPS or TNFalpha, increased PAI-1 release; ascorbate inhibited this increase at low extracellular pH. In unstimulated endothelial cells and platelets, PAI-1 is released into the extracellular space."

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"Tumor necrosis factor alpha (TNF-alpha) is chronically elevated in adipose tissues of obese rodents and humans and has been directly implicated to induce PAI-1 in adipocytes."

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"Endotoxin, IL-1 and tumor necrosis factor have been associated with increased t-PA and PAI-1 mRNA and protein production in cultured en- dothelial cells, while IL-1 and TNF increase PAI-1 synthesis in[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Xanthoangelol (5 and 10 microm) dose-dependently suppressed the TNFa induced PAI-1 increase in the culture medium."

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"Like native GLP-1, liraglutide inhibits tumor necrosis factor alpha (TNF) mediated plasminogen activator inhibitor type-1 (PAI-1) activation in human vascular endothelial cells."

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"Incubation of THLE-5b cells with TNF-alpha stimulated PAI-1 production via protein kinase C-, mitogen activated protein kinase-, protein tyrosine kinase-, and nuclear factor-kappaB-dependent pathways."

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", NK-T cells Kimura et al. (2004) RT Anti-tumor activity: apoptosis (DNA topoisomerase, procasparases-3, -8, -9 in human leukemia (HL60) cells Cytotoxicities: human leukemia (HL60), melanoma (CRL1579), lung cancer (A549), stomach cancer (AZ521) cells Akihisa et al. (2011) ST Cytotoxicities: human neuroblastoma cells (IMR-32, NB-39) Nishimura et al. (2007) RT Anti-hypertensive activity: vasoconstriction in rat aortic rings Matsuura et al. (2001) ST Anti-hypertensive activity: systolic blood pressure in SHRSP Anti-hyperlipidemic activity: serum VLDL (microsomal TG transfer-protein), hepatic TG (differentiation factor 1, fatty acid synthase) levels in SHRSP Ogawa et al. (2005b) AP Anti-diabetic activity: insulin-like activity Enoki et al. (2007) RT Anti-diabetic activity: chronic ingestion on borderline mild hyperglycemia (adiponectin) Ohnogi et al. (2007) RT Anti-diabetic activity: GLUT4 translocation Kawabata et al. (2011) AP Anti-diabetic activity: a-glucosidase Luo et al. (2012) ST Anti-diabetic activity: PTP1B Li et al. (2015) EXD Anti-inflammatory activity (details in the patent) Akihisa et al. (2007) LF Anti-inflammatory activity: IL-6 in TNF-a-stimulated osteosarcoma cells Shin et al. (2011) RT, AP Anti-inflammatory activity: NO, TNF-a, iNOS, COX-2, AP-1 Yasuda et al. (2014), Chang et al. (2014) AP Anti-inflammatory activity: I-jB degradation, NF-jB nuclear translocation Chang et al. (2014) RT Anti-thrombotic activity: platelet aggregation (induced by collagen, platelet-activating factor, phorbol 12-myristate 13-acetate, not thrombin) Son et al. (2014) LF Anti-viral activity: influenza virus neuraminidase Park et al. (2011) WP Anti-viral activity: SARS-CoV (viral proteases: 3CL pro , PL pro ) Park et al. (2015) RT Preventive effect against metabolic syndrome: adiponectin production Ohnogi et al. (2012b) RT Preventive effect against metabolic syndrome: adipocytes differentiation (AMPK, MAPK pathways; C/EBPs, PPARc) Zhang et al. (2013) AP Anti-oxidative activity: NQO1 induction Luo et al. (2012) WP Anti-oxidative activity: XO Kim et al. (2014) ST Whitening activity: melanin formation in B16 melanoma cells Arung et al. (2012) AP Anti-depressant activity: inhibition of MAO-B (selective), DBH Kim et al. (2013) a Plant part code: WP whole plant, RT root, AP aerial part (including stem and leaf), ST stem, LF leaf, EXD exudate; other source code: Syn syntheticAnti-tumor-promoter activity: EBV-EA by TPA Anti-tumor-initiator activity: NOR 1 Akihisa et al. (2003) EXD Anti-inflammatory activity (details in the patent) Akihisa et al. (2007) ST Cytotoxicities: human neuroblastoma (IMR-32, NBisolation from the part Nakata et al. (1999) EXD Anti-tumor-promoter activity: EBV-EA by TPA, in vivo Akihisa et al. (2003) Two-stage mouse skin carcinogenesis test Anti-tumor-initiator activity: NOR 1 Akihisa et al. (2006) ST Anti-tumor activity: apoptosis (procaspase-3, -9, Bax) in human neuroblastoma cells (IMR-32, NB-39) Nishimura et al. (2007) EXD Anti-inflammatory activity (details in the patent) Akihisa et al. (2007) Com Anti-inflammatory activity: iNOS Shin et al. (2013) Syn Anti-bacterial activity: Gram-positive bacteria Sugamoto et al. (2011) AP Anti-oxidative activity: NQO1 induction, DPPH radical scavenging Luo et al. (2012) WP Anti-oxidative activity: XO Kim et al. (2014) AP Anti-diabetic activity: a-glucosidase Luo et al. (2012) WP Anti-viral activity: SARS-CoV (3CL pro , PL pro ) Park et al. -viral activity: influenza virus neuraminidase Park et al. (2011) WP Anti-viral activity: SARS-CoV (3CL pro , PL pro ) Park et al. (2015)4,2 0 -Dihydroxy-3 0 -[(2E)-6-hydroperoxy-3methyl-7-methylene-2-octenyl]-4 0 -methoxy chalcone(7)RT Preventive effect against metabolic syndrome: adiponectin productionOhnogi et al. (2012b)Anti-inflammatory activity: TNF-a induced ET-1 (NF-jB) Sugii et al. (2005) AP Anti-viral activity: influenza virus neuraminidase Park et al. (2011) ST Anti-thrombotic activity: TNFa-induced PAI-1 Ohkura et al. (2011) WP Anti-viral activity: SARS-CoV (3CL pro , PL pro ) Park et al. -inflammatory activity: NO, iNOS, COX-2 (IjB degradation, NF-jB nuclear translocation) Chang et al. (2014) WP Anti-viral activity: SARS-CoV (3CL pro , PL pro ) Park et al. isolation from the part Nakata et al. (1999) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2003) ST Cytotoxicities: human neuroblastoma (IMR-32, NB-39) Nishimura et al. (2007) ST Whitening activity: melanin formation in melanoma cells Arung et al. (2012) Deoxyxanthoangelol H (13) EXD First isolation from the part Akihisa et al. (2006) EXD Anti-inflammatory activity (details in the patent) Akihisa et al. (2007) ST Whitening activity: melanin formation in melanoma cells Arung et al. (2012) Xanthoangelol I (14) EXD Anti-tumor-promoter activity: EBV-EA by TPA Anti-tumor-initiator activity: NOR 1 Akihisa et al. (2006) ST Cytotoxicities: human neuroblastoma (IMR-32, NB-39) Nishimura et al. (2007) 2 00 -Hydroxy-xanthoangelol I (15) RT Protective effect on nerve cells (details in the patent) Onogi et al. (2004) RT Preventive effect against metabolic syndrome: adiponectin Ohnogi et al. (2012b) Xanthoangelol J (16) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. isolation from the part Li et al. (2015)Dorsmannin A (23) EXD First isolation from the partAkihisa et al. (2006)-diabetic activity: PTP1B Li et al. (2015) Luteolin-7-O-b-D-rutinoside (44) AP First isolation from the part Park et al. (1995) AP Anti-mutagenic activity (AFB1) Park et al. (1997a)AP Anti-oxidative activity: DPPH radical scavengingKim et al. (2005)-tumor-promoter activity: EBV-EA by TPAAkihisa et al. (2003) AP Anti-diabetic activity: a-glucosidaseLuo et al. (2012) Munduleaflavanone B (52) EXD Anti-tumor-promoter activity: EBV-EA by TPAAkihisa et al. (2006) Anti-tumor-initiator activity: NOR 1 EXD anti-inflammatory activity: TPA-induced mouse ear edemaAkihisa et al. (2007) Isobavachin(53) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2006) Prostratol F (54) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2003) Sophoraflavanone A (55) (=8geranylnaringenin) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2006) Anti-tumor-initiator activity: NOR 1 EXD Anti-inflammatory activity: TPA-induced mouse ear edema Akihisa et al. (2007) 4 0 -O-Geranylnaringenin (56) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2003) Coumarins Umbelliferone (57) RT First isolation from the part Baba et al. (1990b) Scopoletin (58) RT First isolation from the part Baba et al. (1990b) Demethylsuberosin (59) AP Anti-diabetic activity: a-glucosidase Luo et al. (2012) Osthenol (60) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. (2006) Anti-tumor-initiator activity: NOR 1 EXD Anti-inflammatory activity (details in the patent) Akihisa et al. (2007) 7-O-b-D-Glucopyranosyloxy-8-prenyl coumarinRT First isolation from the partKozawa et al. (1978) FR First isolation from the partBaba et al. 1990a) (3 0 R)-Hydroxy columbianadin(79)(=(8S,9R)-8-angeloyl oxy-8,9-dihydrooroselol) EXD Anti-tumor-promoter activity: EBV-EA by TPA Akihisa et al. isolation from the part Baba et al. (1990b) FR First isolation from the part Baba et al. (1990a) EXD Anti-tumor-initiator activity: NOR 1 Akihisa et al. (2003) EXD Anti-allergic activity: lgE-mediated mast cell activation (bhexosaninidase, LTC4, TNF-a, FceRI b-chain PLCc1, p38 MAPK, IjB-a) Kishiro et al. (2008) AP First isolation from the part Luo et al. (2012) ST Anti-diabetic activity: PTP1B Li et al. (2015)Selidinin(84)EXD Anti-inflammatory activity (details in the patent)Akihisa et al. (2007) Senecioyl khellactone (87) EXD Anti-tumor-promoter activity: EBV-EA by TPAAkihisa et al. (2003) Anti-tumor-initiator activity: NOR 1 AP Anti-diabetic activity: a-glucosidaseLuo et al. (2012)TriterpenesPregnenolone(107)AP Anti-oxidative activity: DPPH radical scavengingLuo et al. (2012)Fig. 1 continued, cynaroside (43, luteolin-7-O-b-D-glucopyranoside), luteolin-7-O-b-D-rutinoside (44), kaempferol-3-O-a-D-arabinopyranoside (46), isoquercitrin (47, quercetin-3-O-b-Dglucopyranoside), hyperoside (48, quercetin-3-O-b-Dgalactopyranoside), quercetin-3-O-a-D-arabinopyranoside (50), pregnenoloneThe reported biological activities of xanthoangelol (1) WP whole plant, RT root, AP aerial part (including stem and leaf), ST stem, LF leaf, EXD exudate; other source code: Syn syntheticConstituents from A. keiskei and their reported biological activitiesWP whole plant, RT root, AP aerial part (including stem and leaf), ST stem, LF leaf, EXD exudate, FR fruit, SD seed; other source code: Syn synthetic, Com commercialFig."

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"Luciferase reporter gene assay showed that hypoxia, TNF-alpha, and their combination increased PAI-1 transcription activity by 1.8-fold, 1.4-fold, and 2.2-fold, respectively."

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"Therefore, these results collectively indicate that the PAI-1 and t-PA ratio was increased by TNF-alpha and significantly decreased by PL compared to TNF-alpha treated conditions (XREF_FIG C)."

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"The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits."

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"TNF is also known to increase levels of PAI-1 , which , in turn , inhibit fibrinolysis [ 18 ] ."

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"TNFα is known to induce PAI-1 [100,101], with one mechanism related to enhancement of NF-kappaB sites of the PAI-1 gene [102]."
| PMC

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"In this study, we investigated the mechanism whereby 1,25 (OH) 2 D 3 counters the induction of PAI-1 by TNFalpha and LPS in mouse embryonic fibroblasts (MEFs)."

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"The PAI-1 promoter is activated by TNF-α via an NFκB 5′ upstream element and directly activated by TGF-β1 via SMAD2/3 promoter binding sites ."

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"Ghrelin, a recently described orexigenic peptide hormone, attenuates PAI-1 induced by TNF-alpha in the human hepatoma cell line (HepG2)."

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"Our findings suggest that some of the major functions of synoviocytes are the production of IL8, TFPI2, PAI1 and FLJ10143 upon stimulation by TNFalpha."

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"During inflammatory events, TNF-alpha and IL-1beta proinflammatory cytokines induce the production of PAI-1, the main plasminogen activator, in vascular ECs."

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"TNF-alpha stimulates PAI-1 synthesis by various cell types in vitro and in vivo [6-10]."

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"TNF-alpha increased PAI-1 synthesis, whereas kallistatin significantly suppressed PAI-1 expression with or without TNF-alpha treatment."

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"TNF-alpha also reduces lipoprotein lipase activity in white adipocytes, stimulates hepatic lipolysis, and increases plasminogen activator inhibitor-1 content in adipocytes."

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"Tumor necrosis factor (TNF) stimulates plasminogen activator inhibitor (PAI) production by endothelial cells and decreases blood fibrinolytic activity in the rat."

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"Furthermore, eckol and dieckol inhibited TNF-alpha induced PAI-1 production and the ratio between PAI-1 and t-PA was found to be significantly decreased by eckol and dieckol."

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"Shear stress and TNF-alpha additively induced PAI-1, whereas shear stress blocked the cytokine effect on t-PA and u-PA."

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"The observations suggest TZDs inhibit TNFalpha mediated PAI-1 induction independent of inducible PPARgamma activation and this may involve in the modulation of Nur77 and Nurr1 expression and NP binding to the PAI-1 NBRE."

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"These results suggest that TNF-alpha and the local renin-angiotensin system coordinately stimulate PAI-1 production in hepatocytes."

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"Collectively, these results indicate that TNF-alpha increased the PAI-1 and t-PA ratio, which was inhibited by compounds 1, 2, and 4 (XREF_FIG)."

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"(1) TNF-alpha or mmLDL could induce PAI-1 activity and mRNA expression in HUVECs."

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"SR-202 treatment had no significant effect on TZD mediated modulation of TNFalpha stimulation of PAI-1 secretion (Figs. 2 A-C), suggesting that these effects are mediated independent of inducible PPAR[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Suboptimal concentrations of ET-1 and tumor necrosis factor-alpha (TNF-alpha) acted synergistically to increase PAI-1 production."

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"Both TNF-alpha and endotoxin significantly increased PAI-1 mRNA in the adipose tissue, peaking at 3-8 h."

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"To identify mechanism (s) through which TNF-alpha induces PAI-1, 3T3-L1 preadipocytes were differentiated into adipocytes and exposed to TNF-alpha for 24 h. TNF-alpha selectively increased the synthesis of PAI-1 without increasing activity of plasminogen activators."

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"Here, we report that the p75 neurotrophin receptor (p75 NTR), a TNF receptor superfamily member up-regulated after tissue injury, blocks fibrinolysis by down-regulating the serine protease, tissue plasminogen activator (tPA), and up-regulating plasminogen activator inhibitor-1 (PAI-1)."

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"Systemic inflammatory TNFα and IL1β can upregulate PAI‐1 synthesis, especially in sepsis‐induced systemic inflammation by gram‐negative bacteremia 76."

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"The main xanthoangelol subtype in Ashitaba was the most potent inhibitor of a TNFa stimulated PAI-1 increase in the culture medium of human EA.hy926 endothelial cells."

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"TNFalpha receptor RI was also actively released and was shown to reduce TNFalpha activity which may account for the inability of soluble TNFalpha to up-regulate PAI-1 synthesis."

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"Thiazolidinediones inhibit TNFalpha induction of PAI-1 independent of PPARgamma activation."

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"The elevated TNFalpha in the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations associated with preeclampsia."

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"The supernatant PAI-1 concentrations in the cells treated with TNF-alpha under normoxic conditions were significantly increased by 1.8-fold at 24 hours, and by 3.1-fold at 48 hours compared with those[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"In conclusion, this study shows that PL inhibits the extrinsic and intrinsic pathways of blood coagulation by inhibiting FXa and thrombin generation and that both inhibit TNF-alpha induced PAI-1 protein secretion by HUVECs."

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"Tumor necrosis factor alpha (TNF-alpha) enhanced PAI-1 secretion and mRNA expression by approximately 2-fold."

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"Although a recent study insists that inhibition of tumor necrosis factor alpha (TNF alpha) does not reduce the induction of PAI-1 by endotoxin in rats, we imagine that TNF alpha is involved in the induction of PAI-1 by endotoxin, because endotoxin treatment induces TNF alpha and administration of TNF alpha induces PAI-1 both in vitro and in vivo."

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"Association of TNF with the agents induced a PAI-1 response that was more than additive of the two, whereas the secretion of uPA was not enhanced."

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"Because induction of PAI-1 by TNF-alpha is potentiated synergistically by insulin, both agonists appear likely to contribute to the impairment of fibrinolytic system capacity typical in obese, hyperinsulinemic patients."

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"WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-alpha induced PAI-1 production."

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"TNFalpha upregulates the expression of Nur77 in human umbilical vein endothelial cells, and in turn, the PAI-1 (plasminogen activator inhibitor 1) promoter contains a Nur77 binding region that mediates the TNFalpha induction of PAI-1 [XREF_BIBR]."

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"The mechanism involved in TNFalpha stimulation of mouse PAI-1, however, remains unknown."

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"TZDs decreased basal and TNF stimulated PAI-1 secretion and mRNA expression in HUVECs in a dose dependent fashion [XREF_BIBR, XREF_BIBR]."

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"Simvastatin also attenuated the increase in expression and secretion of PAI-1 induced by TNF-alpha (16898.6 +/- 1663.3 vs 12922.1 +/- 843.9 and 5.19 +/- 3.12 vs 0.59 +/- 0.16, respectively p < 0.05), but under baseline conditions had no effect on the expression or secretion of PAI-1."

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"This is further strong evidence supporting the hypothesis that TZDs modify TNFalpha stimulated secretion of PAI-1 independent of inducible PPARgamma activation."

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"Taken together, these observations indicate that liraglutide inhibits TNF- or glucose mediated induction of PAI-1 and vascular adhesion molecule expression, and this effect may involve the modulation of NUR77."

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"This study tested the hypothesis that EGCG might have an inhibitory effect on PAI-1 production induced by TNF-alpha."

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"Not only hypercoagulability but also anticoagulant protein reduction contributes to thrombosis in this setting : protein C is decreased for consumption; TF pathway inhibitor (TFPI) production is impaired and is also rapidly consumed, while fibrinolysis is compromised because of endothelial PAI-1 hyperproduction stimulated by IL-1 and TNF-alpha [XREF_BIBR, XREF_BIBR, XREF_BIBR]; Vrij et coll."

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"Reactive oxygen species and TNF-alpha can promote the release of PAI-1 and promote cell necrosis via the activation of inflammatory responses, which further helps in the release of IL-1alpha, a factor responsible for neutrophil infiltration."

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"PAI-1 production is increased by TNF-alpha and IL-1."

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"Treatment of CB6 mice with LPS, TNF-alpha, or transforming growth factor-beta (TGF-beta) increased the steady-state levels of PAI-1 mRNA within 3 h in all tissues examined."

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"We show that activation of PAI-1 gene by TNFalpha and reactive oxygen species is mediated by interaction of NF-kappaB with the cis-acting element located in the -675 4G/5G insertion/deletion in the PAI-1 promoter."

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"Indeed, decidual (XREF_FIG) as well as EVT derived (XREF_FIG) factors such as transforming growth factors (TGFs), Nodal, or tumour necrosis factor alpha (TNFalpha) were shown to elevate TIMP or PAI expression XREF_BIBR."

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"TNF alone induced a more marked accumulation of PAI-1 than of uPA."

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"However, injection of these mice with TNF-alpha increased PAI-1 mRNA in a tissue specific pattern strikingly similar to that observed in LPS treated CB6 mice."

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"IL-1β and TNF-α augment the activity of tissue factor and plasminogen activator inhibitor-1 (PAI-1) and may contribute to hypercoagulability (53, 54)."

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"In dose and time-course studies, HLF plasminogen activator inhibitor-1 (PAI-1) was increased by TGF-beta, whereas TNF-alpha induced release of PAI-1 into the media."

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"TNF also induced a marked increase of PAI-1 messenger RNA (mRNA) in the cells."

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"Enzyme linked immunosorbent assay of culture media showed that TNF-alpha (10 ng/mL) increased PAI-1 secretion by 4.2 fold compared with control (105.5 +/- 9.6) versus 24.9 +/- 1.7 ng/mL, n = 3)."

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"These statins modestly inhibited TNFalpha induced PAI-1 accumulation in the culture medium."

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"In this study, we used 3T3-L1 adipocytes to examine the mechanism by which TNF-alpha up-regulates PAI-1 in the adipocyte."

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"Studies also show that LPS and TNF upregulate PAI-1 through an NF-kappaB-dependent pathway."

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"The MAPKK inhibitor (PD98059, 60 mumol/L) could markedly inhibit PAI-1 activity and mRNA expression induced by TNF-alpha (100 U/ml) or mmLDL (50 micrograms/ml)."

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"Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFalpha), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed."

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"We show that activation of PAI-1 gene by TNFalpha and reactive oxygen species is mediated by interaction of NF-kappaB with the cis-acting element located in the -675 4G/5G insertion/deletion in the PAI-1 promoter."

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"This pilot study tested the hypothesis that TNF-alpha blockade with pentoxifylline lowers PAI-1 and high-sensitivity CRP (hsCRP) in obese individuals."

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"However, TNF-alpha increased PAI-1 release by 2.8-fold in spite of a small increase in the intracellular ceramide levels (approx."

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"Furthermore, phloroglucinol inhibited TNF-alpha induced PAI-1 production."

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"As shown in XREF_FIG A, PL dose-dependently inhibited TNF-alpha induced PAI-1 secretion from HUVECs, and this decrease became significant at a PL dose of 10 muM."

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"Modulation of PAI-1 and proMMP-9 syntheses by soluble TNFalpha and its receptors during differentiation of the human monocytic HL-60 cell line."

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"Acute (3 h) and chronic (24 h) exposure of 3T3-L1 adipocytes to TNF-alpha induces PAI-1 mRNA by increasing the rate of transcription of the PAI-1 gene, and de novo protein synthesis is not required for this process."

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"Exposure to TNF-alpha (10 ng/ml) significantly increased the PAI-1 and t-PA ratio for both cell types, with a larger effect on SMCs."

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"We identified a 5 ' distal TNFalpha responsive enhancer of the PAI-1 gene located 15 kb upstream of the transcription start site containing a conserved NFkappaB binding site that mediates the response to TNFalpha."

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"Parathyroid hormone (PTH), prostaglandin E2, (PGE2) or tumor necrosis factor alpha (TNF-alpha) enhanced the secretion of urokinase-type plasminogen activator (u-PA) antigen and suppressed the secretion of plasminogen activator inhibitor-1 (PAI-1) antigen to the conditioned medium."

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"However, treatment with oleate mostly prevented the elevation of PAI-1 induced by TNF-alpha."