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Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

Liu W, Chen Q, Wu S, Xia X, Wu A, Cui F, Gu YP, Zhang X, Cao J - J. Radiat. Res. (2015)

Bottom Line: PGN-treated irradiated mice showed an increase in CD45(+)CD34(+) cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05).The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway.Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.

View Article: PubMed Central - PubMed

Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.

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Related in: MedlinePlus

Treatment with PGN and WR-2721 in combination normalized ileum villus height and number of crypts after 10 Gy WBI. N = unirradiated mice, IR = 10 Gy WBI mice, P = 10 Gy WBI mice treated with PGN, W = WR-2721-treated 10 Gy WBI mice, P + W = PGN and WR-2721 combination-treated 10 Gy WBI mice (original magnification ×200). After 10 Gy WBI the small intestine became vacuolated, villus height was clearly shortened, and half or fewer of the crypts remained. On Day 1.25 post IR, villus height and number of crypts in the P and W groups group had not changed obviously compared with the IR group, and marked differences could be observed in comparison with the N group. However, on Day 4 post-IR, the P + W group had longer villi and more crypts compared with the IR group (*P < 0.05), while the P and W groups were unchanged. Error bars indicate the SD for n = 10 mice.
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RRU100F3: Treatment with PGN and WR-2721 in combination normalized ileum villus height and number of crypts after 10 Gy WBI. N = unirradiated mice, IR = 10 Gy WBI mice, P = 10 Gy WBI mice treated with PGN, W = WR-2721-treated 10 Gy WBI mice, P + W = PGN and WR-2721 combination-treated 10 Gy WBI mice (original magnification ×200). After 10 Gy WBI the small intestine became vacuolated, villus height was clearly shortened, and half or fewer of the crypts remained. On Day 1.25 post IR, villus height and number of crypts in the P and W groups group had not changed obviously compared with the IR group, and marked differences could be observed in comparison with the N group. However, on Day 4 post-IR, the P + W group had longer villi and more crypts compared with the IR group (*P < 0.05), while the P and W groups were unchanged. Error bars indicate the SD for n = 10 mice.

Mentions: Histological changes in the ilea were characterized by the adherence of submucosal layers and sloughing of crypts, as well as ulcers and ruptured villi in 10 Gy irradiated mice (Fig. 3). Irradiated animals that received either WR-2721 or PGN evidently had longer villi and more crypts compared with untreated irradiated mice four days after 10 Gy IR (Fig. 3). Furthermore, irradiated mice treated with a combination of PGN and WR2721 had normal mucosal thickness, minimal inflammatory changes, and preserved tissue architecture.Fig. 3.


Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

Liu W, Chen Q, Wu S, Xia X, Wu A, Cui F, Gu YP, Zhang X, Cao J - J. Radiat. Res. (2015)

Treatment with PGN and WR-2721 in combination normalized ileum villus height and number of crypts after 10 Gy WBI. N = unirradiated mice, IR = 10 Gy WBI mice, P = 10 Gy WBI mice treated with PGN, W = WR-2721-treated 10 Gy WBI mice, P + W = PGN and WR-2721 combination-treated 10 Gy WBI mice (original magnification ×200). After 10 Gy WBI the small intestine became vacuolated, villus height was clearly shortened, and half or fewer of the crypts remained. On Day 1.25 post IR, villus height and number of crypts in the P and W groups group had not changed obviously compared with the IR group, and marked differences could be observed in comparison with the N group. However, on Day 4 post-IR, the P + W group had longer villi and more crypts compared with the IR group (*P < 0.05), while the P and W groups were unchanged. Error bars indicate the SD for n = 10 mice.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380048&req=5

RRU100F3: Treatment with PGN and WR-2721 in combination normalized ileum villus height and number of crypts after 10 Gy WBI. N = unirradiated mice, IR = 10 Gy WBI mice, P = 10 Gy WBI mice treated with PGN, W = WR-2721-treated 10 Gy WBI mice, P + W = PGN and WR-2721 combination-treated 10 Gy WBI mice (original magnification ×200). After 10 Gy WBI the small intestine became vacuolated, villus height was clearly shortened, and half or fewer of the crypts remained. On Day 1.25 post IR, villus height and number of crypts in the P and W groups group had not changed obviously compared with the IR group, and marked differences could be observed in comparison with the N group. However, on Day 4 post-IR, the P + W group had longer villi and more crypts compared with the IR group (*P < 0.05), while the P and W groups were unchanged. Error bars indicate the SD for n = 10 mice.
Mentions: Histological changes in the ilea were characterized by the adherence of submucosal layers and sloughing of crypts, as well as ulcers and ruptured villi in 10 Gy irradiated mice (Fig. 3). Irradiated animals that received either WR-2721 or PGN evidently had longer villi and more crypts compared with untreated irradiated mice four days after 10 Gy IR (Fig. 3). Furthermore, irradiated mice treated with a combination of PGN and WR2721 had normal mucosal thickness, minimal inflammatory changes, and preserved tissue architecture.Fig. 3.

Bottom Line: PGN-treated irradiated mice showed an increase in CD45(+)CD34(+) cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05).The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway.Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.

View Article: PubMed Central - PubMed

Affiliation: School of Radiation Medicine and Protection, Soochow University, No. 199 Ren'ai Road, Suzhou 215123, PR China.

Show MeSH
Related in: MedlinePlus