ผลต่างระหว่างรุ่นของ "หน้าหลัก"
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| − | + | Ration on NEC development [146]. Consistent with these findings, the administration of | |
| + | Ration on NEC improvement [146]. Constant with these findings, the administration with the phosphodiesterase-5 inhibitor sildenafil to keep intraluminal nitric oxide activity [151] also markedly reduces NEC severity [146], when eNOS deficient mice demonstrated a considerably elevated NEC phenotype. These findings confirm the significance of endothelial nitric oxide regulation in NEC pathogenesis, and may clarify why infant formula ?which is deficient in nitrate ?may possibly predispose for the improvement of this illness.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptCellular regulation of TLR4 signaling as a therapeutic target in NECHaving shown that TLR4 activation plays a pivotal role within the development of NEC, the query emerges as to no matter if TLR4 and its connected downstream pathways can serve as preventive or therapeutic targets against NEC. Under, we are going to summarize current research that have attempted to answer this query. i. Intracellular inhibitor, heat shock protein 70 (HSP70) HSP70 is definitely an essential member with the heat shock protein family, that is strongly upregulated by several environmental stressors such as heat, but in addition reactive oxygen species [152, 153], ultraviolet light [154], -irradiation [155] and chemical substances [156]. We've not too long ago shown that HSP70 is down-regulated inside the inflamed intestine in NEC [157], when other individuals have reported that HSP70 is decreased in IBD [158]. In in search of to know the function of HSP70 down-regulation in NEC, we showed that intracellular HSP70 induction in enterocytes up-regulates co-chaperone carboxyl-terminus of HSP70 interacting proteinPathophysiology. Author manuscript; readily available in PMC 2015 February 01.Lu and HackamPagemediated ubiquitination of TLR4, which leads to the proteasomal degradation of TLR4, and subsequently a down-regulation of NEC severity [157]. Importantly, we showed that the administration in the cell permeable triterpenoid antioxidant celastrol led to the pharmacologic induction of intracellular HSP70 [159, 160], which inhibited TLR4 signaling within the intestinal epithelium and attenuated NEC severity [157]. Glutamine, certainly one of the nonessential amino acids, protects against gut injury and promotes mucosal healing by way of HSP70 induction [161], and glutamine treatment is related with TLR4 down-regulation [162]. Interestingly, glutamine supplementation was shown to reduces the histologic evidence of hypoxia-reoxygenation-induced intestinal injury in experimental NEC [163], and was recommended to possess beneficial effects on intestinal integrity as well as the all round incidence of NEC in preterm infants [164]. ii. Inhibition of Notch signaling It has been suggested that improved luminal bile acids [165], abnormal bile acid metabolism [147] and dysregulated bile acid transporters [166, 167] contribute to NEC by way of dampening goblet cell differentiation and decreasing mucin Muc2 expression in premature ileum [148]. We further showed that bile acids activated Notch signaling plays a part in the development of NEC [66]. These findings recommend that the inhibition of Notch signaling could serve as a preventive or therapeutic target in patients with NEC. In help of this possibility, the administration of dibenzazepine, a pharmacologic inhibitor of -secretase and Notch signaling [168], was identified to markedly enhance the number of goblet cells within the premature intestine and to for that reason considerably cut down NEC severity [66]. These findings raise the possibility that sma. | ||
รุ่นแก้ไขเมื่อ 14:11, 29 มิถุนายน 2564
Ration on NEC development [146]. Consistent with these findings, the administration of Ration on NEC improvement [146]. Constant with these findings, the administration with the phosphodiesterase-5 inhibitor sildenafil to keep intraluminal nitric oxide activity [151] also markedly reduces NEC severity [146], when eNOS deficient mice demonstrated a considerably elevated NEC phenotype. These findings confirm the significance of endothelial nitric oxide regulation in NEC pathogenesis, and may clarify why infant formula ?which is deficient in nitrate ?may possibly predispose for the improvement of this illness.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptCellular regulation of TLR4 signaling as a therapeutic target in NECHaving shown that TLR4 activation plays a pivotal role within the development of NEC, the query emerges as to no matter if TLR4 and its connected downstream pathways can serve as preventive or therapeutic targets against NEC. Under, we are going to summarize current research that have attempted to answer this query. i. Intracellular inhibitor, heat shock protein 70 (HSP70) HSP70 is definitely an essential member with the heat shock protein family, that is strongly upregulated by several environmental stressors such as heat, but in addition reactive oxygen species [152, 153], ultraviolet light [154], -irradiation [155] and chemical substances [156]. We've not too long ago shown that HSP70 is down-regulated inside the inflamed intestine in NEC [157], when other individuals have reported that HSP70 is decreased in IBD [158]. In in search of to know the function of HSP70 down-regulation in NEC, we showed that intracellular HSP70 induction in enterocytes up-regulates co-chaperone carboxyl-terminus of HSP70 interacting proteinPathophysiology. Author manuscript; readily available in PMC 2015 February 01.Lu and HackamPagemediated ubiquitination of TLR4, which leads to the proteasomal degradation of TLR4, and subsequently a down-regulation of NEC severity [157]. Importantly, we showed that the administration in the cell permeable triterpenoid antioxidant celastrol led to the pharmacologic induction of intracellular HSP70 [159, 160], which inhibited TLR4 signaling within the intestinal epithelium and attenuated NEC severity [157]. Glutamine, certainly one of the nonessential amino acids, protects against gut injury and promotes mucosal healing by way of HSP70 induction [161], and glutamine treatment is related with TLR4 down-regulation [162]. Interestingly, glutamine supplementation was shown to reduces the histologic evidence of hypoxia-reoxygenation-induced intestinal injury in experimental NEC [163], and was recommended to possess beneficial effects on intestinal integrity as well as the all round incidence of NEC in preterm infants [164]. ii. Inhibition of Notch signaling It has been suggested that improved luminal bile acids [165], abnormal bile acid metabolism [147] and dysregulated bile acid transporters [166, 167] contribute to NEC by way of dampening goblet cell differentiation and decreasing mucin Muc2 expression in premature ileum [148]. We further showed that bile acids activated Notch signaling plays a part in the development of NEC [66]. These findings recommend that the inhibition of Notch signaling could serve as a preventive or therapeutic target in patients with NEC. In help of this possibility, the administration of dibenzazepine, a pharmacologic inhibitor of -secretase and Notch signaling [168], was identified to markedly enhance the number of goblet cells within the premature intestine and to for that reason considerably cut down NEC severity [66]. These findings raise the possibility that sma.
