PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 20060890-0 2010 Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 56-64 20060890-6 2010 Simvastatin inhibited the DNA binding and transcriptional activities of NFkappaB resulting in marked reduction in transcription of Bcl(XL). Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 72-80 20060890-10 2010 Importantly, simvastatin markedly prevented binding of NFkappaB to the two canonical recognition elements, NFRE-1 and NFRE-2 present in the PTEN promoter. Simvastatin 13-24 nuclear factor kappa B subunit 1 Homo sapiens 55-63 20060890-13 2010 Taken together, our data present a novel bifaceted mechanism where simvastatin acts on a nodal transcription factor NFkappaB, which attenuates the expression of anti-apoptotic Bcl(XL) and simultaneously derepresses the expression of anti-proliferative/proapoptotic tumor suppressor PTEN to prevent breast cancer cell growth. Simvastatin 67-78 nuclear factor kappa B subunit 1 Homo sapiens 116-124 18698233-5 2008 METHODS AND RESULTS: In cells expressing the 299D-399T TLR4, LPS activated the transcription factor NFkappaB and increased the expression of interleukin-6 and tumor necrosis factor-alpha, and these effects were reduced by pretreatment of the cells with pravastatin or simvastatin. Simvastatin 268-279 nuclear factor kappa B subunit 1 Homo sapiens 100-108 19008785-8 2009 Our data suggest that simvastatin, despite lowering circulating low-density lipoprotein cholesterol, decreased LPS toxicity by reduction of NF-kappaB activation and subsequent release of TNF by modulating 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and therefore deserves consideration as a possible adjuvant therapy in acute inflammatory disease. Simvastatin 22-33 nuclear factor kappa B subunit 1 Homo sapiens 140-149 18036510-1 2008 We recently found that simvastatin can modulate the nuclear factor-kappaB (NF-kappaB) activation pathway, but whether other statins have similar effects to those of simvastatin is unknown. Simvastatin 23-34 nuclear factor kappa B subunit 1 Homo sapiens 75-84 18036510-5 2008 Simvastatin suppressed the NF-kappaB activation and potentiated the apoptosis induced by doxorubicin, paclitaxel, and 5-fluorouracil. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 27-36 16515553-10 2006 Simvastatin reversed the inhibition of NF-kappaB activity induced by OGD/reoxygenation or HNE. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 39-48 18036510-1 2008 We recently found that simvastatin can modulate the nuclear factor-kappaB (NF-kappaB) activation pathway, but whether other statins have similar effects to those of simvastatin is unknown. Simvastatin 23-34 nuclear factor kappa B subunit 1 Homo sapiens 52-73 17644777-3 2007 In the present study, atorvastatin and simvastatin dose-dependently decreased LPL and EL expression as well as Rho, liver X receptor alpha (LXRalpha), and nuclear factor kappaB (NF-kappaB) activation in THP-1 macrophages. Simvastatin 39-50 nuclear factor kappa B subunit 1 Homo sapiens 178-187 17729120-6 2007 The NF-kappaB was activated by the LT-treatment and was further enhanced by simvastatin, pravastatin or Y27632 addition. Simvastatin 76-87 nuclear factor kappa B subunit 1 Homo sapiens 4-13 17317725-10 2007 Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. Simvastatin 84-95 nuclear factor kappa B subunit 1 Homo sapiens 32-40 17197385-10 2007 Intriguingly, simvastatin (10 microM) down-regulated HIV-Tat-induced ET-1 and also inhibited activation of NF-kappaB in astrocytes. Simvastatin 14-25 nuclear factor kappa B subunit 1 Homo sapiens 107-116 17464346-11 2007 Simvastatin (0.1, 0.5, or 2.5 micromol/L) markedly inhibited the elevated concentrations of TNF-alpha and sICAM-1, the activity of NF-kappaB, and the phosphorylation of p38 MAPK and ERK(1/2) induced by ADMA. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 131-140 16515553-11 2006 The neuroprotection by simvastatin was significantly attenuated by various NF-kappaB inhibitors, implying that simvastatin inhibits the cytotoxicity of HNE at least in part by maintaining the activity of NF-kappaB. Simvastatin 23-34 nuclear factor kappa B subunit 1 Homo sapiens 75-84 16515553-11 2006 The neuroprotection by simvastatin was significantly attenuated by various NF-kappaB inhibitors, implying that simvastatin inhibits the cytotoxicity of HNE at least in part by maintaining the activity of NF-kappaB. Simvastatin 23-34 nuclear factor kappa B subunit 1 Homo sapiens 204-213 16515553-11 2006 The neuroprotection by simvastatin was significantly attenuated by various NF-kappaB inhibitors, implying that simvastatin inhibits the cytotoxicity of HNE at least in part by maintaining the activity of NF-kappaB. Simvastatin 111-122 nuclear factor kappa B subunit 1 Homo sapiens 75-84 16515553-11 2006 The neuroprotection by simvastatin was significantly attenuated by various NF-kappaB inhibitors, implying that simvastatin inhibits the cytotoxicity of HNE at least in part by maintaining the activity of NF-kappaB. Simvastatin 111-122 nuclear factor kappa B subunit 1 Homo sapiens 204-213 12753293-7 2003 Luciferase reporter gene assays and Western blot analysis in human fibrosarcoma HT1080 cells and HMC were performed to analyze the effect of simvastatin on the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate tissue factor gene expression. Simvastatin 141-152 nuclear factor kappa B subunit 1 Homo sapiens 182-204 15821443-5 2005 Atorvastatin or simvastatin decreased NF-kappa B activation induced by oxidative stress by around 50% in both cell types and was correlated with the I kappa B-alpha levels. Simvastatin 16-27 nuclear factor kappa B subunit 1 Homo sapiens 38-48 12753293-14 2003 Also, simvastatin reduced NF-kappa B- and AP-1-dependent reporter gene activity in TNF-alpha-treated HT-1080 fibrosarcoma cells and reduced the nuclear levels of p50-NF-kappa B, p65-NF-kappa B, and the AP-1 components c-fos and c-jun in HMC. Simvastatin 6-17 nuclear factor kappa B subunit 1 Homo sapiens 26-36 12753293-14 2003 Also, simvastatin reduced NF-kappa B- and AP-1-dependent reporter gene activity in TNF-alpha-treated HT-1080 fibrosarcoma cells and reduced the nuclear levels of p50-NF-kappa B, p65-NF-kappa B, and the AP-1 components c-fos and c-jun in HMC. Simvastatin 6-17 nuclear factor kappa B subunit 1 Homo sapiens 162-165 12753293-7 2003 Luciferase reporter gene assays and Western blot analysis in human fibrosarcoma HT1080 cells and HMC were performed to analyze the effect of simvastatin on the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), which regulate tissue factor gene expression. Simvastatin 141-152 nuclear factor kappa B subunit 1 Homo sapiens 206-216 12753293-14 2003 Also, simvastatin reduced NF-kappa B- and AP-1-dependent reporter gene activity in TNF-alpha-treated HT-1080 fibrosarcoma cells and reduced the nuclear levels of p50-NF-kappa B, p65-NF-kappa B, and the AP-1 components c-fos and c-jun in HMC. Simvastatin 6-17 nuclear factor kappa B subunit 1 Homo sapiens 166-176 29604489-7 2018 Accordingly, the TNF-induced elevation of neutrophil p50 activity was abolished by simvastatin. Simvastatin 83-94 nuclear factor kappa B subunit 1 Homo sapiens 53-56 12753293-14 2003 Also, simvastatin reduced NF-kappa B- and AP-1-dependent reporter gene activity in TNF-alpha-treated HT-1080 fibrosarcoma cells and reduced the nuclear levels of p50-NF-kappa B, p65-NF-kappa B, and the AP-1 components c-fos and c-jun in HMC. Simvastatin 6-17 nuclear factor kappa B subunit 1 Homo sapiens 166-176 31924353-12 2021 Simvastatin attenuated TLR4-dependent NF-kappaB signaling and down-regulated TLR4 levels. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 38-47 31924353-13 2021 CONCLUSIONS: Simvastatin prevented TLR4-induced osteogenic phenotypic changes in isolated aortic valve interstitial cells via down-regulation of TLR4 and inhibition of NF-kappaB signaling. Simvastatin 13-24 nuclear factor kappa B subunit 1 Homo sapiens 168-177 32706497-7 2020 Inhibiting NO production and ROS generation using N-acetylcysteine (NAC) and L-NG-monomethyl arginine acetate (L-NMMA), respectively, accelerated the influence of simvastatin on NF-kappaB activity. Simvastatin 163-174 nuclear factor kappa B subunit 1 Homo sapiens 178-187 32706497-10 2020 Our findings suggested that simvastatin blocks COX-2 expression by inhibiting SNP-induced NO production and IL-1beta-induced ROS generation by blocking the NF-kappaB pathway. Simvastatin 28-39 nuclear factor kappa B subunit 1 Homo sapiens 156-165 31070532-0 2018 Effect of simvastatin on the SIRT2/NF-kappaB pathway in rats with acute pulmonary embolism. Simvastatin 10-21 nuclear factor kappa B subunit 1 Homo sapiens 35-44 31070532-2 2018 OBJECTIVE: The current article studies the effect of simvastatin on the SIRT2/NF-kappaB pathway in rats with APE. Simvastatin 53-64 nuclear factor kappa B subunit 1 Homo sapiens 78-87 31070532-9 2018 CONCLUSIONS: Simvastatin protects against APE-induced pulmonary artery pressure, hypoxemia and inflammatory changes probably due to the regulation of SIRT2/NF-kappaB signalling pathway, which suggest that simvastatin may have promising protective effects in patients with APE. Simvastatin 13-24 nuclear factor kappa B subunit 1 Homo sapiens 156-165 31070532-9 2018 CONCLUSIONS: Simvastatin protects against APE-induced pulmonary artery pressure, hypoxemia and inflammatory changes probably due to the regulation of SIRT2/NF-kappaB signalling pathway, which suggest that simvastatin may have promising protective effects in patients with APE. Simvastatin 205-216 nuclear factor kappa B subunit 1 Homo sapiens 156-165 12524225-3 2003 METHODS AND RESULTS: Simvastatin, atorvastatin, and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). Simvastatin 21-32 nuclear factor kappa B subunit 1 Homo sapiens 141-163 12524225-3 2003 METHODS AND RESULTS: Simvastatin, atorvastatin, and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). Simvastatin 21-32 nuclear factor kappa B subunit 1 Homo sapiens 165-174 35123844-8 2022 Phosphorylation of MAPKs and NF-kappab was evaluated by Western blot after treatment with TNF-alpha, IL-1beta, oxidized LDL, and simvastatin. Simvastatin 129-140 nuclear factor kappa B subunit 1 Homo sapiens 29-38 35123844-11 2022 Western blot analysis showed that oxidized LDL as well as TNF-alpha and IL-1beta activated the signaling of MAPKs and NF-kappab in LF cells, and that simvastatin treatment reduced the phosphorylation of all signaling. Simvastatin 150-161 nuclear factor kappa B subunit 1 Homo sapiens 118-127 32633363-0 2020 Simvastatin induces apoptosis of nasopharyngeal carcinoma cells through NF-kappaB signaling pathway. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 72-81 32633363-14 2020 Further studies demonstrated that simvastatin remarkably attenuated the Luciferase activity of pNF-kappaB-Luc, thereby specifically inhibiting the NF-kappaB signaling pathway. Simvastatin 34-45 nuclear factor kappa B subunit 1 Homo sapiens 96-105 32633363-15 2020 CONCLUSIONS: Simvastatin inhibits proliferation and promotes apoptosis of NPC cells by inhibiting the NF-kappaB pathway. Simvastatin 13-24 nuclear factor kappa B subunit 1 Homo sapiens 102-111 31934265-11 2019 After pretreatment with NAC, the phosphorylation of P38MAPK, JNK, and NF-kappaB and TGF-beta expressions in ECs under stretch was suppressed; similar results were observed in simvastatin-treated ECs. Simvastatin 175-186 nuclear factor kappa B subunit 1 Homo sapiens 70-79 29872377-6 2018 Mechanistic studies revealed that 6-OHDA-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/p38 mitogen-activated protein kinase (MAPK) pathway was inhibited and nuclear factor-kappaB (NF-kappaB) nuclear transcription decreased in SH-SY5Y cells after simvastatin treatment. Simvastatin 282-293 nuclear factor kappa B subunit 1 Homo sapiens 193-214 29604489-0 2018 Attenuation of TNF-induced neutrophil adhesion by simvastatin is associated with the inhibition of Rho-GTPase activity, p50 activity and morphological changes. Simvastatin 50-61 nuclear factor kappa B subunit 1 Homo sapiens 120-123 29604489-9 2018 Simvastatin appears to inhibit neutrophil adhesion by interfering in TNF-induced cytoskeletal rearrangements, in association with the inhibition of Rho A activity, NFkappaB translocation and, consequently, beta2-integrin activity. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 164-172 26574150-9 2016 Furthermore, pretreatment with simvastatin inhibited the LPS-induced EMT in BECs by downregulating NF-kappaB and JNK phosphorylation. Simvastatin 31-42 nuclear factor kappa B subunit 1 Homo sapiens 99-108 28910332-0 2017 Concurrent treatment with simvastatin and NF-kappaB inhibitor in human castration-resistant prostate cancer cells exerts synergistic anti-cancer effects via control of the NF-kappaB/LIN28/let-7 miRNA signaling pathway. Simvastatin 26-37 nuclear factor kappa B subunit 1 Homo sapiens 172-181 28910332-12 2017 Our data illustrate that simvastatin remarkably inhibits the growth of human CRPC cells by suppressing NF-kappaB and LIN28B and subsequently upregulating let-7 miRNAs. Simvastatin 25-36 nuclear factor kappa B subunit 1 Homo sapiens 103-112 26911804-0 2016 Simvastatin in combination with bergamottin potentiates TNF-induced apoptosis through modulation of NF-kappaB signalling pathway in human chronic myelogenous leukaemia. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 100-109 26574150-11 2016 CONCLUSIONS: Our results demonstrate that LPS or TGF-beta1 promote the EMT in BECs that that pretreatment with simvastatin inhibited the induced EMT by downregulating toll-like receptor 4 and NF-kappaB phosphorylation. Simvastatin 111-122 nuclear factor kappa B subunit 1 Homo sapiens 192-201 25738368-6 2015 In addition, simvastatin decreased the protein expression of matrix metalloproteinase (MMP)-2 and suppressed the activation of nuclear factor (NF)-kappaB in the MDA-MB-231 cells. Simvastatin 13-24 nuclear factor kappa B subunit 1 Homo sapiens 127-153 25738368-7 2015 Taken together, these results demonstrated that the antitumor effect of simvastatin in the human MDA-MB-231 breast cancer cell line was via the inhibition of cell proliferation, affecting the cell cycle, downregulating the expression levels of cyclin D1 and CDKs, inducing apoptosis and decreasing the expression of MMP-2, possibly by inhibiting the activation of NF-kappaB. Simvastatin 72-83 nuclear factor kappa B subunit 1 Homo sapiens 364-373 25978361-14 2015 In conclusion, Simvastatin and benznidazole prevent endothelial activation induced by T. cruzi infection, and the effect of simvastatin is mediated by the inhibition of the NFkappaB pathway by inducing 15-epi-LXA4 production. Simvastatin 124-135 nuclear factor kappa B subunit 1 Homo sapiens 173-181 25547946-3 2015 We examined the in vitro effects of three HMG-CoA reductase inhibitors atorvastatin, simvastatin, and pravastatin on the viability of MSCs and expression of nuclear factor kappa B (NF-kappaB). Simvastatin 85-96 nuclear factor kappa B subunit 1 Homo sapiens 157-179 25547946-5 2015 Human MSC treatment with 1 and 10 muM simvastatin or atorvastatin resulted in progressively reduced cell viability, which was associated with a decline in NF-kappaB p65. Simvastatin 38-49 nuclear factor kappa B subunit 1 Homo sapiens 155-164 25013486-0 2014 Suppressive effects of simvastatin on the human acute promyelocytic leukemia NB4 cell line through the regulation of the nuclear factor-kappaB signaling pathway. Simvastatin 23-34 nuclear factor kappa B subunit 1 Homo sapiens 121-142 25316568-0 2014 Simvastatin induces NFkappaB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 20-28 25316568-3 2014 Simvastatin-induced Pin1 down-regulation evoked NFkappaB/p65 degradation. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 48-56 25013486-3 2014 Changes were noted in the expression levels of 56 genes involved in the NF-kappaB signaling pathways in the NB4 cells treated with 15 mum simvastatin at 48 h post-incubation, among which, 47 genes were downregulated and 9 were upregulated. Simvastatin 138-149 nuclear factor kappa B subunit 1 Homo sapiens 72-81 25013486-1 2014 The present study examined the effects of simvastatin on the proliferation, apoptosis and gene expression levels involved in the nuclear factor-kappaB (NF-kappaB) signaling pathway in the human acute promyelocytic leukemia NB4 cell line by methyl thiazolyl tetrazolium assay, flow cytometry and the Human NF-kappaB Signaling Pathway RT2 Profiler PCR Array profiles. Simvastatin 42-53 nuclear factor kappa B subunit 1 Homo sapiens 129-150 25013486-4 2014 In conclusion, simvastatin potentially inhibits the proliferation and induces the apoptosis of NB4 cells through the regulation of the expression levels of genes involved in the NF-kappaB signaling pathway. Simvastatin 15-26 nuclear factor kappa B subunit 1 Homo sapiens 178-187 25013486-1 2014 The present study examined the effects of simvastatin on the proliferation, apoptosis and gene expression levels involved in the nuclear factor-kappaB (NF-kappaB) signaling pathway in the human acute promyelocytic leukemia NB4 cell line by methyl thiazolyl tetrazolium assay, flow cytometry and the Human NF-kappaB Signaling Pathway RT2 Profiler PCR Array profiles. Simvastatin 42-53 nuclear factor kappa B subunit 1 Homo sapiens 152-161 24392131-0 2014 Systemic simvastatin rescues retinal ganglion cells from optic nerve injury possibly through suppression of astroglial NF-kappaB activation. Simvastatin 9-20 nuclear factor kappa B subunit 1 Homo sapiens 119-128 24233024-4 2014 The effect of simvastatin on the proliferation of gastric cancer cells was examined by mitochondrial dye-uptake 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, apoptosis by esterase staining, NF-kappaB activation by DNA binding assay, and protein expression by western blot analysis. Simvastatin 14-25 nuclear factor kappa B subunit 1 Homo sapiens 213-222 24233024-6 2014 Simvastatin suppressed the proliferation of gastric cancer cells, enhanced the apoptotic effects of capecitabine, suppressed the constitutive activation of NF-kappaB, and abrogated the expression of cyclooxygenase-2 (COX-2), cyclin D1, Bcl-2, survivin, CXC motif receptor 4, and MMP-9 proteins. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 156-165 24233024-8 2014 As compared to the vehicle control, simvastatin also suppressed the expression of NF-kappaB-regulated gene products such as cyclin D1, COX-2, ICAM-1, MMP-9, survivin, Bcl-xL, and XIAP in tumor tissues. Simvastatin 36-47 nuclear factor kappa B subunit 1 Homo sapiens 82-91 24233024-9 2014 Overall, our results demonstrate that simvastatin can enhance the effects of capecitabine through suppression of NF-kappaB-regulated markers of proliferation, invasion, angiogenesis, and metastasis. Simvastatin 38-49 nuclear factor kappa B subunit 1 Homo sapiens 113-122 24392131-13 2014 Simvastatin (1.0 microM) significantly reduced the TNF-alpha-induced NF-kappaB activation in cultured optic nerve astrocytes. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 69-78 24392131-14 2014 We conclude that systemic simvastatin can reduce the death of RGCs induced by crushing the optic nerve possibly by suppressing astroglial NF-kappaB activation. Simvastatin 26-37 nuclear factor kappa B subunit 1 Homo sapiens 138-147 23794945-6 2013 The highest reduction could be seen after treatment with irbesartan and simvastatin in combination (all P<0.001).There were strongly positive correlations between AngII or CVF with PDGF, Rac1, NF-kappaB, and among PDGF, Rac1 and NF-kappaB (all P<0.05). Simvastatin 72-83 nuclear factor kappa B subunit 1 Homo sapiens 196-205 23794945-6 2013 The highest reduction could be seen after treatment with irbesartan and simvastatin in combination (all P<0.001).There were strongly positive correlations between AngII or CVF with PDGF, Rac1, NF-kappaB, and among PDGF, Rac1 and NF-kappaB (all P<0.05). Simvastatin 72-83 nuclear factor kappa B subunit 1 Homo sapiens 232-241 23794945-7 2013 CONCLUSIONS: Irbesartan or/and simvastatin can improve atrial fibrosis by regulating PDGF/Rac1/NF-kappaB axis. Simvastatin 31-42 nuclear factor kappa B subunit 1 Homo sapiens 95-104 23762985-2 2013 Simvastatin at a concentration of 100 ng/ml increases p50 (the blood pO2 corresponding to its 50% oxygen saturation) at real values of pH and pCO2 from 39.53 + 2.41 (p <0.05) to 36.60 (36, 40, 37, 60) (p <0.05) mm Hg. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 54-57 22633472-11 2012 CONCLUSION: High dose simvastatin therapy reduces proinflammatory transcription factor NF-kappaB binding activity and hsCRP levels, while combination of low dose simvastatin with ezetimibe resulting in a similar LDL-reduction does not affect these inflammatory markers. Simvastatin 22-33 nuclear factor kappa B subunit 1 Homo sapiens 87-96 22694979-0 2012 Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-kappaB. Simvastatin 0-11 nuclear factor kappa B subunit 1 Homo sapiens 94-103 22694979-7 2012 NF-kappaB expression was lower (p = 0.018) in the simvastatin group. Simvastatin 50-61 nuclear factor kappa B subunit 1 Homo sapiens 0-9 22694979-9 2012 CONCLUSION: Simvastatin inhibits free radicals and TNF-alpha generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-kappaB activity. Simvastatin 12-23 nuclear factor kappa B subunit 1 Homo sapiens 168-177