scholarly journals CpG-Oligodeoxynucleotides Improved Irradiation-Induced Injuries by G-CSF and IL-6 Up-Regulation

2017 ◽  
Vol 44 (6) ◽  
pp. 2368-2377 ◽  
Author(s):  
Pei Zhang ◽  
Suhe Dong ◽  
Jiaming Guo ◽  
Yanyong Yang ◽  
Cong Liu ◽  
...  
Keyword(s):  
Survival Rate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interferon Α ◽  
Radioprotective Property ◽  
Granulocyte Colony Stimulating Factor ◽  
Cpg Oligodeoxynucleotides ◽  
Underlying Mechanisms ◽  
Radioprotective Properties ◽  
Stimulating Factor ◽  
Different Doses

Background/Aims: This study investigated the radioprotective properties of three classes of CpG-oligodeoxynucleotides (CpG-ODNs) and the underlying mechanisms. Methods: Mice irradiated at different doses(7Gy or 9Gy) were treated with or without ODNs(50μg via intraperitoneal injection). Assays were performed to determine survival rate and the number of white blood cell in peripheral blood. The levels of granulocyte-colony stimulating factor(G-CSF), interleukin 6(IL-6) and interferon-α (IFN-α) were measured using enzyme-linked immunosorbent assay (ELISA). Results: Survival rate of mice irradiated in 7Gy was increased from 50% to about 100% with ODNs pretreatment. ODNs administration increased the number of WBCs of irradiated mice. G-CSF, IL-6 and IFN-α levels were up-regulated with ODNs treatment. Conclusion: All three classes of ODNs protected mice from irradiation-induced injuries. B-class ODNs exhibited the most potent radioprotective property via the up-regulation of G-CSF and IL-6.

scholarly journals Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Feiyan Zhao ◽  
Wei Liu ◽  
Shaojie Yue ◽  
Lei Yang ◽  
Qingzhong Hua ◽  
...  
Keyword(s):  
Cxcr4 Expression ◽  
Pathological Examination ◽  
Akt Pathway ◽  
Granulocyte Colony Stimulating Factor ◽  
Akt Phosphorylation ◽  
Antifibrotic Effect ◽  
Marrow Mesenchymal Stem Cells ◽  
Underlying Mechanisms ◽  
Stimulating Factor

Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.

scholarly journals In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 638-645 ◽  
Author(s):  
FM Uckun ◽  
L Souza ◽  
KG Waddick ◽  
M Wick ◽  
CW Song
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Conclusive Evidence ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Regimens ◽  
Stimulating Factor

Abstract The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.

In vivo radioprotective effects of recombinant human granulocyte colony- stimulating factor in lethally irradiated mice

Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 638-645 ◽  
Author(s):  
FM Uckun ◽  
L Souza ◽  
KG Waddick ◽  
M Wick ◽  
CW Song
Keyword(s):  
Survival Rate ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Conclusive Evidence ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Regimens ◽  
Stimulating Factor

The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.

scholarly journals Effects of Drug Concentration, Rate of Infusion, and Flush Volume on G-CSF Drug Loss When Administered Intravenously

2018 ◽  
Vol 54 (6) ◽  
pp. 393-397
Author(s):  
Pirun Saelue ◽  
Warunsuda Sripakdee ◽  
Krit Suknuntha
Keyword(s):  
Infusion Rate ◽  
Final Concentration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Granulocyte Colony Stimulating Factor ◽  
Percent Recovery ◽  
Drug Loss ◽  
Solution Methods ◽  
Csf Concentration ◽  
Infusion Tube ◽  
Stimulating Factor

Purpose: This study evaluated factors that affect granulocyte-colony stimulating factor (G-CSF) adsorption in the infusion tube by measuring the G-CSF concentration, rate of G-CSF infusion, and volume of flush solution. Methods: The concentrations of G-CSF in all samples were measured by an enzyme-linked immunosorbent assay (ELISA) using human G-CSF Quantikine® ELISA kits. The concentration of G-CSF, the rate of administration, and the volume of flush solution were studied respectively. The concentration of G-CSF and the rate of administration that had a significantly lower G-CSF percent recovery after the infusion via the infusion set were used for further investigation in the study. All samples were diluted with 5% dextrose in water (D5W) to the final concentration within the standard concentration range. All experiments were performed in triplicate. Results: The concentration of G-CSF that was administered through the infusion tube at 20 µg/mL was a significantly higher G-CSF percent recovery compared with the G-CSF concentrations of 5, 10, and 15 µg/mL. The infusion rate of 15 and 20 mL/h percent recovery of G-CSF adsorption was significantly higher than the infusion rates of 30 and 40 mL/h. The concentration of G-CSF at 15 µg/mL and an infusion rate of 30 mL/h were selected to investigate the flush volumes of D5W on G-CSF adsorption. The D5W flush volume of 40 mL dramatically decreased the G-CSF adsorption with a recovery of 103 ± 1.73%. Conclusion: The G-CSF concentration of 20 µg/mL with an infusion rate of 20 mL/h, using a 40 mL D5W flush, was appropriate for intravenous G-CSF administration.

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