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Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
by
Yang, Cheng
, Liu, Aifen
, Wu, Jing
, Nicholson, Michael L.
, Wu, Yuanyuan
, Wang, Wei
, Zhang, Yufang
, Zhang, Yiwen
, Liu, Feng
, Yang, Bin
, Fan, Yaping
, Zhu, Tongyu
in
Albumin
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ CASP-3
/ Caspase 3 - genetics
/ Caspase Inhibitors - pharmacology
/ Caspase-3
/ Cell cycle
/ Cell Line
/ Creatinine
/ cyclic helix B peptide
/ Cyclosporine - pharmacology
/ cyclosporine A
/ Cyclosporins
/ Disease Models, Animal
/ Epithelial cells
/ Erythropoietin
/ Erythropoietin - chemistry
/ Erythropoietin - pharmacology
/ Fibrosis
/ HMGB1 protein
/ Immunohistochemistry
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ ischemia–reperfusion injury
/ Kidney - blood supply
/ Kidney - drug effects
/ Kidney - injuries
/ Kidney transplants
/ Macrophages - drug effects
/ Macrophages - pathology
/ Male
/ Metabolism
/ Mice
/ Mice, Inbred BALB C
/ p70 S6 kinase
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Reperfusion
/ Reperfusion Injury - pathology
/ Reperfusion Injury - prevention & control
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ RNA, Small Interfering - genetics
/ siRNA
/ TOR protein
/ Urine
2021
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Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
by
Yang, Cheng
, Liu, Aifen
, Wu, Jing
, Nicholson, Michael L.
, Wu, Yuanyuan
, Wang, Wei
, Zhang, Yufang
, Zhang, Yiwen
, Liu, Feng
, Yang, Bin
, Fan, Yaping
, Zhu, Tongyu
in
Albumin
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ CASP-3
/ Caspase 3 - genetics
/ Caspase Inhibitors - pharmacology
/ Caspase-3
/ Cell cycle
/ Cell Line
/ Creatinine
/ cyclic helix B peptide
/ Cyclosporine - pharmacology
/ cyclosporine A
/ Cyclosporins
/ Disease Models, Animal
/ Epithelial cells
/ Erythropoietin
/ Erythropoietin - chemistry
/ Erythropoietin - pharmacology
/ Fibrosis
/ HMGB1 protein
/ Immunohistochemistry
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ ischemia–reperfusion injury
/ Kidney - blood supply
/ Kidney - drug effects
/ Kidney - injuries
/ Kidney transplants
/ Macrophages - drug effects
/ Macrophages - pathology
/ Male
/ Metabolism
/ Mice
/ Mice, Inbred BALB C
/ p70 S6 kinase
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Reperfusion
/ Reperfusion Injury - pathology
/ Reperfusion Injury - prevention & control
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ RNA, Small Interfering - genetics
/ siRNA
/ TOR protein
/ Urine
2021
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Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
by
Yang, Cheng
, Liu, Aifen
, Wu, Jing
, Nicholson, Michael L.
, Wu, Yuanyuan
, Wang, Wei
, Zhang, Yufang
, Zhang, Yiwen
, Liu, Feng
, Yang, Bin
, Fan, Yaping
, Zhu, Tongyu
in
Albumin
/ Animals
/ Antibodies
/ Apoptosis
/ Apoptosis - drug effects
/ CASP-3
/ Caspase 3 - genetics
/ Caspase Inhibitors - pharmacology
/ Caspase-3
/ Cell cycle
/ Cell Line
/ Creatinine
/ cyclic helix B peptide
/ Cyclosporine - pharmacology
/ cyclosporine A
/ Cyclosporins
/ Disease Models, Animal
/ Epithelial cells
/ Erythropoietin
/ Erythropoietin - chemistry
/ Erythropoietin - pharmacology
/ Fibrosis
/ HMGB1 protein
/ Immunohistochemistry
/ Immunology
/ Inflammation
/ Injuries
/ Ischemia
/ ischemia–reperfusion injury
/ Kidney - blood supply
/ Kidney - drug effects
/ Kidney - injuries
/ Kidney transplants
/ Macrophages - drug effects
/ Macrophages - pathology
/ Male
/ Metabolism
/ Mice
/ Mice, Inbred BALB C
/ p70 S6 kinase
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Reperfusion
/ Reperfusion Injury - pathology
/ Reperfusion Injury - prevention & control
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ RNA, Small Interfering - genetics
/ siRNA
/ TOR protein
/ Urine
2021
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Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
Journal Article
Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
2021
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Overview
Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Animals
/ CASP-3
/ Caspase Inhibitors - pharmacology
/ Erythropoietin - pharmacology
/ Fibrosis
/ Injuries
/ Ischemia
/ Male
/ Mice
/ Peptide Fragments - chemistry
/ Peptide Fragments - pharmacology
/ Peptides, Cyclic - chemistry
/ Peptides, Cyclic - pharmacology
/ Reperfusion Injury - pathology
/ Reperfusion Injury - prevention & control
/ RNA, Small Interfering - genetics
/ siRNA
/ Urine
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