Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways
Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumato...
Ausführliche Beschreibung
Autor*in: |
El-Ghafar, Omnia Ahmed Mohamed Abd [verfasserIn] Helal, Gouda Kamel [verfasserIn] Abo-Youssef, Amira M. [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Inflammopharmacology - Cham : Springer International Publishing AG, 1991, 28(2020), 5 vom: 05. März, Seite 1253-1267 |
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Übergeordnetes Werk: |
volume:28 ; year:2020 ; number:5 ; day:05 ; month:03 ; pages:1253-1267 |
Links: |
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DOI / URN: |
10.1007/s10787-020-00693-8 |
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Katalog-ID: |
SPR041145240 |
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520 | |a Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. | ||
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700 | 1 | |a Helal, Gouda Kamel |e verfasserin |4 aut | |
700 | 1 | |a Abo-Youssef, Amira M. |e verfasserin |4 aut | |
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10.1007/s10787-020-00693-8 doi (DE-627)SPR041145240 (SPR)s10787-020-00693-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.38 bkl El-Ghafar, Omnia Ahmed Mohamed Abd verfasserin aut Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 Helal, Gouda Kamel verfasserin aut Abo-Youssef, Amira M. verfasserin aut Enthalten in Inflammopharmacology Cham : Springer International Publishing AG, 1991 28(2020), 5 vom: 05. März, Seite 1253-1267 (DE-627)329558315 (DE-600)2047989-X 1568-5608 nnns volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 https://dx.doi.org/10.1007/s10787-020-00693-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 ASE AR 28 2020 5 05 03 1253-1267 |
spelling |
10.1007/s10787-020-00693-8 doi (DE-627)SPR041145240 (SPR)s10787-020-00693-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.38 bkl El-Ghafar, Omnia Ahmed Mohamed Abd verfasserin aut Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 Helal, Gouda Kamel verfasserin aut Abo-Youssef, Amira M. verfasserin aut Enthalten in Inflammopharmacology Cham : Springer International Publishing AG, 1991 28(2020), 5 vom: 05. März, Seite 1253-1267 (DE-627)329558315 (DE-600)2047989-X 1568-5608 nnns volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 https://dx.doi.org/10.1007/s10787-020-00693-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 ASE AR 28 2020 5 05 03 1253-1267 |
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10.1007/s10787-020-00693-8 doi (DE-627)SPR041145240 (SPR)s10787-020-00693-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.38 bkl El-Ghafar, Omnia Ahmed Mohamed Abd verfasserin aut Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 Helal, Gouda Kamel verfasserin aut Abo-Youssef, Amira M. verfasserin aut Enthalten in Inflammopharmacology Cham : Springer International Publishing AG, 1991 28(2020), 5 vom: 05. März, Seite 1253-1267 (DE-627)329558315 (DE-600)2047989-X 1568-5608 nnns volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 https://dx.doi.org/10.1007/s10787-020-00693-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 ASE AR 28 2020 5 05 03 1253-1267 |
allfieldsGer |
10.1007/s10787-020-00693-8 doi (DE-627)SPR041145240 (SPR)s10787-020-00693-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.38 bkl El-Ghafar, Omnia Ahmed Mohamed Abd verfasserin aut Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 Helal, Gouda Kamel verfasserin aut Abo-Youssef, Amira M. verfasserin aut Enthalten in Inflammopharmacology Cham : Springer International Publishing AG, 1991 28(2020), 5 vom: 05. März, Seite 1253-1267 (DE-627)329558315 (DE-600)2047989-X 1568-5608 nnns volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 https://dx.doi.org/10.1007/s10787-020-00693-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 ASE AR 28 2020 5 05 03 1253-1267 |
allfieldsSound |
10.1007/s10787-020-00693-8 doi (DE-627)SPR041145240 (SPR)s10787-020-00693-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.38 bkl El-Ghafar, Omnia Ahmed Mohamed Abd verfasserin aut Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 Helal, Gouda Kamel verfasserin aut Abo-Youssef, Amira M. verfasserin aut Enthalten in Inflammopharmacology Cham : Springer International Publishing AG, 1991 28(2020), 5 vom: 05. März, Seite 1253-1267 (DE-627)329558315 (DE-600)2047989-X 1568-5608 nnns volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 https://dx.doi.org/10.1007/s10787-020-00693-8 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA SSG-OPC-PHA SSG-OPC-ASE GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 ASE AR 28 2020 5 05 03 1253-1267 |
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Enthalten in Inflammopharmacology 28(2020), 5 vom: 05. März, Seite 1253-1267 volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 |
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Enthalten in Inflammopharmacology 28(2020), 5 vom: 05. März, Seite 1253-1267 volume:28 year:2020 number:5 day:05 month:03 pages:1253-1267 |
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Inflammopharmacology |
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El-Ghafar, Omnia Ahmed Mohamed Abd @@aut@@ Helal, Gouda Kamel @@aut@@ Abo-Youssef, Amira M. @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR041145240</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519092043.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s10787-020-00693-8</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR041145240</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s10787-020-00693-8-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.38</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">El-Ghafar, Omnia Ahmed Mohamed Abd</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. 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El-Ghafar, Omnia Ahmed Mohamed Abd |
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El-Ghafar, Omnia Ahmed Mohamed Abd ddc 610 bkl 44.38 misc Rheumatoid arthritis misc Fxa misc JAK2/STAT3 pathway misc MAPK pathway Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways |
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610 ASE 44.38 bkl Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways Rheumatoid arthritis (dpeaa)DE-He213 Fxa (dpeaa)DE-He213 JAK2/STAT3 pathway (dpeaa)DE-He213 MAPK pathway (dpeaa)DE-He213 |
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ddc 610 bkl 44.38 misc Rheumatoid arthritis misc Fxa misc JAK2/STAT3 pathway misc MAPK pathway |
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Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways |
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apixaban exhibits anti-arthritic effects by inhibiting activated factor x-mediated jak2/stat3 and mapk phosphorylation pathways |
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Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways |
abstract |
Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. |
abstractGer |
Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. |
abstract_unstemmed |
Abstract Activated factor X (FXa) is strongly linked to various inflammatory events. This study aimed to investigate the effect of FXa on janus kinase2/signal transducers and activators of transcription3 (JAK2/STAT3) and mitogen-activated protein kinase (MAPK) phosphorylation in relation to rheumatoid arthritis (RA). It also extends its scope to explore the possible anti-arthritic effects of apixaban, a selective FXa inhibitor. Rats were allocated into normal control; complete Freund's adjuvant (CFA, 0.4 ml/4 days/12 days); FXa (120 µg/kg/day/3 days) and CFA + FXa groups as well as three treated groups including CFA + apixaban; FXa + apixaban and CFA + FXa + apixaban. Apixaban was administered at a dose of 10 mg/kg/12 h for15 days. By the end of the experimental period, tissue samples were collected for the assessment of phosphorylated (p)-JAK2, STAT3, MAPK, matrixmetalloprotein-1 (MMP-1) and protease-activated receptor 2. Furthermore, Serum interleukin-6 (IL-6), platelet-derived growth factor (PDGF), anti-citrullinated protein antibody (ACPA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma level of FXa and prothrombin time were evaluated. In support, histopathological and macroscopical examinations were performed. FXa activated JAK2, STAT3 and MAPK phosphorylation through activation of PAR 2, PDGF and IL-6 and concomitantly led to a significant elevation in ACPA, MMP-1 and 8-OHdG. Apixaban markedly amended FXa-induced changes. Conclusively, the current study revealed that FXa may have a drastic role in RA progression and pathogenesis at least through stimulation of JAK2/STAT3 and MAPK phosphorylation. Furthermore, apixaban exerted robust arthro-protective effects. These beneficial outcomes could be attributed to its ability to impede JAK2/STAT3 and MAPK activation, as well as to its antioxidant property. |
collection_details |
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container_issue |
5 |
title_short |
Apixaban exhibits anti-arthritic effects by inhibiting activated factor X-mediated JAK2/STAT3 and MAPK phosphorylation pathways |
url |
https://dx.doi.org/10.1007/s10787-020-00693-8 |
remote_bool |
true |
author2 |
Helal, Gouda Kamel Abo-Youssef, Amira M. |
author2Str |
Helal, Gouda Kamel Abo-Youssef, Amira M. |
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hochschulschrift_bool |
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doi_str |
10.1007/s10787-020-00693-8 |
up_date |
2024-07-03T20:30:09.290Z |
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|
score |
7.4006405 |