The Experts below are selected from a list of 183381 Experts worldwide ranked by ideXlab platform
Josef Neu - One of the best experts on this subject based on the ideXlab platform.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice
Nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Abstract Objectives Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Methods Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7–12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12–17). Mouse pups received Arg-Gln (5 g · kg −1 · d −1 ) or DHA (5 g · kg −1 · d −1 ) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. Results The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. Conclusion The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice.
Nutrition (Burbank Los Angeles County Calif.), 2012Co-Authors: Xueyan Liu, Maria B. Grant, Lynn Shaw, Sergio Li Calzi, Josef NeuAbstract:Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7-12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12-17). Mouse pups received Arg-Gln (5 g · kg⁻¹ · d⁻¹) or DHA (5 g · kg⁻¹ · d⁻¹) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants. Copyright © 2012 Elsevier Inc. All rights reserved.
-
Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuates Hyperoxia-induced Small Intestinal Injury in Neonatal Mice
Journal of pediatric gastroenterology and nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Background and Objective Supplementation studies of glutamine, argi-nine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model.
-
380 Dietary Arg-Gln Dipeptide or Dha Reduces Pathological Neovascularization (NV) and Promotes Retinal Vessel Re-Growth (VR) in Mouse Model of Rop
Pediatric Research, 2010Co-Authors: S. Li Calzi, Lynn C Shaw, Julia V. Busik, Kristin Morris, Josef Neu, Maria B. GrantAbstract:Aims: ROP is the leading cause of blindness in children. The most abundant sphingolipid in retinal membranes, sphingomyelin (S), is converted to ceramide (C) by acid sphingomyelinase; C/S ratio indicates inflammation and retinal injury. We compared the effects of Arg-Gln dipeptide, alone or with DHA on NV, VR and C/S ratio in a model of ROP. Methods: 7-day old pups and their nursing dams were placed in 75% oxygen for five days. Pups were returned to room air on postnatal day 12 (P12) and supplemented by oral gavage twice daily with Arg- Gln (5 g/kg/d), DHA (2.5 g/kg/d), Arg-Gln + DHA, or vehicle through P17. On P17, pups were sacrificed and perfused with FITC-labeled dextran. Retinas were assessed for NV by enumeration of pre-retinal endothelial cells, intra-retinal vascular density (VR) or C/S ratio by MS. Results: Compared to vehicle, pre-retinal NV was reduced by 61% and 51% with Arg-Gln or DHA (p< 0.05 both), with a 69% reduction observed for Arg- Gln + DHA (p< 0.05). All treatments reduced vasoobliteration vs. vehicle (32% vs. 5.2%, p< 0.05). Arg-Gln, alone or with DHA, promoted intra-retinal vascular density (VR) vs. vehicle (73-76% vs. 53%). Arg-Gln returned retinal C/S ratio to that of control. Conclusion: These results demonstrate the dietary supplementation with Arg-Gln, alone or with DHA, reduces pre-retinal NV and promotes VR in a model of ROP, underscoring the importance of nutrition in modulating disease course. In addition, C/S ratio was normalized by Arg-Gln, supporting a key role for Arg-Gln in reducing acid sphingomyelinase.
-
The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.
Investigative ophthalmology & visual science, 2006Co-Authors: Josef Neu, Lynn C Shaw, Aqeela Afzal, Hao Pan, Esteban Gallego, Sergio Li Calzi, Sergio Caballero, P.e. Spoerri, Maria B. GrantAbstract:PURPOSE. Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS. The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by realtime RT-PCR. RESULTS. Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82% 7% (P 0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64% 9% (P 0.001). CONCLUSIONS. Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP. (Invest Ophthalmol
Maria B. Grant - One of the best experts on this subject based on the ideXlab platform.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice
Nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Abstract Objectives Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Methods Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7–12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12–17). Mouse pups received Arg-Gln (5 g · kg −1 · d −1 ) or DHA (5 g · kg −1 · d −1 ) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. Results The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. Conclusion The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice.
Nutrition (Burbank Los Angeles County Calif.), 2012Co-Authors: Xueyan Liu, Maria B. Grant, Lynn Shaw, Sergio Li Calzi, Josef NeuAbstract:Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7-12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12-17). Mouse pups received Arg-Gln (5 g · kg⁻¹ · d⁻¹) or DHA (5 g · kg⁻¹ · d⁻¹) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants. Copyright © 2012 Elsevier Inc. All rights reserved.
-
Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuates Hyperoxia-induced Small Intestinal Injury in Neonatal Mice
Journal of pediatric gastroenterology and nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Background and Objective Supplementation studies of glutamine, argi-nine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model.
-
380 Dietary Arg-Gln Dipeptide or Dha Reduces Pathological Neovascularization (NV) and Promotes Retinal Vessel Re-Growth (VR) in Mouse Model of Rop
Pediatric Research, 2010Co-Authors: S. Li Calzi, Lynn C Shaw, Julia V. Busik, Kristin Morris, Josef Neu, Maria B. GrantAbstract:Aims: ROP is the leading cause of blindness in children. The most abundant sphingolipid in retinal membranes, sphingomyelin (S), is converted to ceramide (C) by acid sphingomyelinase; C/S ratio indicates inflammation and retinal injury. We compared the effects of Arg-Gln dipeptide, alone or with DHA on NV, VR and C/S ratio in a model of ROP. Methods: 7-day old pups and their nursing dams were placed in 75% oxygen for five days. Pups were returned to room air on postnatal day 12 (P12) and supplemented by oral gavage twice daily with Arg- Gln (5 g/kg/d), DHA (2.5 g/kg/d), Arg-Gln + DHA, or vehicle through P17. On P17, pups were sacrificed and perfused with FITC-labeled dextran. Retinas were assessed for NV by enumeration of pre-retinal endothelial cells, intra-retinal vascular density (VR) or C/S ratio by MS. Results: Compared to vehicle, pre-retinal NV was reduced by 61% and 51% with Arg-Gln or DHA (p< 0.05 both), with a 69% reduction observed for Arg- Gln + DHA (p< 0.05). All treatments reduced vasoobliteration vs. vehicle (32% vs. 5.2%, p< 0.05). Arg-Gln, alone or with DHA, promoted intra-retinal vascular density (VR) vs. vehicle (73-76% vs. 53%). Arg-Gln returned retinal C/S ratio to that of control. Conclusion: These results demonstrate the dietary supplementation with Arg-Gln, alone or with DHA, reduces pre-retinal NV and promotes VR in a model of ROP, underscoring the importance of nutrition in modulating disease course. In addition, C/S ratio was normalized by Arg-Gln, supporting a key role for Arg-Gln in reducing acid sphingomyelinase.
-
The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.
Investigative ophthalmology & visual science, 2006Co-Authors: Josef Neu, Lynn C Shaw, Aqeela Afzal, Hao Pan, Esteban Gallego, Sergio Li Calzi, Sergio Caballero, P.e. Spoerri, Maria B. GrantAbstract:PURPOSE. Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS. The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by realtime RT-PCR. RESULTS. Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82% 7% (P 0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64% 9% (P 0.001). CONCLUSIONS. Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP. (Invest Ophthalmol
Lynn C Shaw - One of the best experts on this subject based on the ideXlab platform.
-
Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity.
Investigative ophthalmology & visual science, 2018Co-Authors: Lynn C Shaw, Sergio Li Calzi, Leni Moldovan, Nilanjana Sengupta-caballero, Judith Quigley, Mircea Ivan, Bokkyoo Jun, Nicolas G. Bazan, Michael E. BoultonAbstract:Purpose Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). Results With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Conclusions Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice
Nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Abstract Objectives Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Methods Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7–12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12–17). Mouse pups received Arg-Gln (5 g · kg −1 · d −1 ) or DHA (5 g · kg −1 · d −1 ) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. Results The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. Conclusion The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants.
-
Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuates Hyperoxia-induced Small Intestinal Injury in Neonatal Mice
Journal of pediatric gastroenterology and nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Background and Objective Supplementation studies of glutamine, argi-nine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model.
-
380 Dietary Arg-Gln Dipeptide or Dha Reduces Pathological Neovascularization (NV) and Promotes Retinal Vessel Re-Growth (VR) in Mouse Model of Rop
Pediatric Research, 2010Co-Authors: S. Li Calzi, Lynn C Shaw, Julia V. Busik, Kristin Morris, Josef Neu, Maria B. GrantAbstract:Aims: ROP is the leading cause of blindness in children. The most abundant sphingolipid in retinal membranes, sphingomyelin (S), is converted to ceramide (C) by acid sphingomyelinase; C/S ratio indicates inflammation and retinal injury. We compared the effects of Arg-Gln dipeptide, alone or with DHA on NV, VR and C/S ratio in a model of ROP. Methods: 7-day old pups and their nursing dams were placed in 75% oxygen for five days. Pups were returned to room air on postnatal day 12 (P12) and supplemented by oral gavage twice daily with Arg- Gln (5 g/kg/d), DHA (2.5 g/kg/d), Arg-Gln + DHA, or vehicle through P17. On P17, pups were sacrificed and perfused with FITC-labeled dextran. Retinas were assessed for NV by enumeration of pre-retinal endothelial cells, intra-retinal vascular density (VR) or C/S ratio by MS. Results: Compared to vehicle, pre-retinal NV was reduced by 61% and 51% with Arg-Gln or DHA (p< 0.05 both), with a 69% reduction observed for Arg- Gln + DHA (p< 0.05). All treatments reduced vasoobliteration vs. vehicle (32% vs. 5.2%, p< 0.05). Arg-Gln, alone or with DHA, promoted intra-retinal vascular density (VR) vs. vehicle (73-76% vs. 53%). Arg-Gln returned retinal C/S ratio to that of control. Conclusion: These results demonstrate the dietary supplementation with Arg-Gln, alone or with DHA, reduces pre-retinal NV and promotes VR in a model of ROP, underscoring the importance of nutrition in modulating disease course. In addition, C/S ratio was normalized by Arg-Gln, supporting a key role for Arg-Gln in reducing acid sphingomyelinase.
-
The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.
Investigative ophthalmology & visual science, 2006Co-Authors: Josef Neu, Lynn C Shaw, Aqeela Afzal, Hao Pan, Esteban Gallego, Sergio Li Calzi, Sergio Caballero, P.e. Spoerri, Maria B. GrantAbstract:PURPOSE. Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS. The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by realtime RT-PCR. RESULTS. Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82% 7% (P 0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64% 9% (P 0.001). CONCLUSIONS. Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP. (Invest Ophthalmol
Yadong Wang - One of the best experts on this subject based on the ideXlab platform.
-
Updated assessment of the association of the XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population.
Asian Pacific journal of cancer prevention : APJCP, 2015Co-Authors: Haiyan Yang, Haiyu Wang, Si-yu Yang, Fu-ye Shao, Yadong WangAbstract:Background Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and methods Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.97- 1.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.
-
Updated Assessment of the Association of the XRCC1 Arg399Gln Polymorphism with Lung Cancer Risk in the
2015Co-Authors: Haiyan Yang, Haiyu Wang, Si-yu Yang, Fu-ye Shao, Yadong WangAbstract:Background: Published studies have reported relationships between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and lung cancer risk in Chinese population. However, the epidemiological results remained controversial. The objective of this study was to clarify the association of XRCC1 Arg399Gln polymorphism with lung cancer risk in the Chinese population. Materials and Methods: Systematic searches were performed through the database of Medline/Pubmed, Web of Science, Embase, CNKI and WanFang Medical Online. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated to estimate the strength of the association. Results: Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.36, 95%CI: 1.09-1.71) in the Chinese population on the basis of 19 studies with 5,416 cases and 5,782 controls. We did not observe any association between XRCC1 codon 399 Arg/Gln and Arg/Gln+Gln/Gln polymorphisms and lung cancer risk (OR=1.00, 95%CI: 0.92-1.08 and OR=1.05, 95%CI: 0.971.13, respectively). Limiting the analysis to studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Gln/Gln genotype (OR=1.18, 95%CI: 1.01-1.38). When stratified by source of control, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 399 Arg/Gln+Gln/Gln genotype on the basis of hospitalized patient-based controls (OR=1.21, 95%CI: 1.04-1.42) and among subjects carrying XRCC1 codon 399 Gln/Gln genotype on the basis of healthy subject-based controls (OR=1.22, 95%CI: 1.04-1.43). Conclusions: Our findings indicated that certain XRCC1 Arg399Gln variants might affect the susceptibility of lung cancer in Chinese population. Larger sample size studies are required to confirm our findings.
-
An updated meta-analysis on the association of X-ray repair cross complementing group 1 codon 399 polymorphism with hepatocellular carcinoma risk.
Asian Pacific journal of cancer prevention : APJCP, 2014Co-Authors: Yadong Wang, Wenlong Zhai, Haiyu Wang, Xiang-qun XiaAbstract:Background: A number of studies have reported the association of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with susceptibility to hepatocellular carcinoma (HCC). However, the results were inconsistent and inconclusive. The aim of this study was to comprehensively explore the association of XRCC1 Arg399Gln variant with HCC risk. Materials and Methods: Systematic searches of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database were performed. Pooled odds ratio (OR) with 95% confidence intervals (CI) was calculated to estimate the strength of association. Results: Overall, we observed an increased HCC risk among subjects carrying XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotypes (OR=1.20, 95%CI: 1.05-1.38, OR=1.16, 95%CI: 1.05-1.28, and OR=1.14, 95%CI: 1.04-1.24, respectively) based on 20 studies including 3374 cases and 4633 controls. In subgroup analysis, we observed an increased risk of XRCC1 codon 399 Gln/Gln, Arg/Gln and Gln/Gln+Arg/Gln polymorphisms for HCC in hospital-based study (OR=1.25, 95%CI: 1.03-1.51, OR=1.21, 95%CI: 1.07-1.36 and OR=1.18, 95%CI: 1.06-1.31, respectively) and in Asian population (OR=1.19, 95%CI: 1.03-1.38, OR=1.17, 95%CI: 1.04-1.30 and OR=1.14, 95%CI: 1.04-1.25, respectively). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased HCC risk among Gln/Gln, Arg/Gln and Gln/ Gln+Arg/Gln genotype carriers (OR=1.17, 95%CI: 1.05-1.29, OR=1.12, 95%CI: 1.00-1.25 and OR=1.11, 95%CI: 1.02-1.21, respectively). Conclusions: This updated meta-analysis results suggest that XRCC1 Arg399Gln variants may contribute to HCC risk. Well-designed studies with larger sample size were required to further verify our findings.
-
Association of X-ray repair cross complementing group 1 Arg399Gln polymorphisms with the risk of squamous cell carcinoma of the head and neck: evidence from an updated meta-analysis.
PloS one, 2013Co-Authors: Yadong Wang, Xinwei Chu, Xiaojing Meng, Fei ZouAbstract:Background Epidemiologic studies have reported the association of X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln polymorphisms with susceptibility to squamous cell carcinoma of the head and neck (HNSCC). However, the results were conflictive rather than conclusive. The purpose of this study was to clarify the association of XRCC1 Arg399Gln variants with HNSCC risk. Methods Systematic searches were performed through the search engines of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database. Summary odds ratio (OR) with 95% confidence intervals (CI) was computed to estimate the strength association. Results Overall, we did not observe any association of XRCC1 Arg399Gln polymorphisms with HNSCC risk in total population (OR = 0.95, 95% CI: 0.76–1.19 for Gln/Gln vs. Arg/Arg, OR = 1.05, 95% CI: 0.92–1.20 for Arg/Gln vs. Arg/Arg, and OR = 1.03, 95% CI: 0.90–1.18 for Gln/Gln+Arg/Gln vs. Arg/Arg) based on 18 studies including 3917 cases and 4560 controls. In subgroup analyses, we observed an increased risk of XRCC1 399 Arg/Gln genotype for HNSCC in Caucasians (OR = 1.20, 95% CI: 1.00–1.44) and Gln/Gln genotype for larynx squamous cell carcinoma (OR = 1.63, 95% CI: 1.10–2.40). We did not observe any association between XRCC1 Arg399Gln variants and HNSCC risk in additional subgroup analyses. Conclusion The results from this present meta-analysis suggest that XRCC1 Arg399Gln variants may contribute to HNSCC risk among Caucasians and to the risk of larynx squamous cell carcinoma. Further, well-designed studies with larger sample sizes are required to verify our findings.
Sergio Li Calzi - One of the best experts on this subject based on the ideXlab platform.
-
Enteral Arg-Gln Dipeptide Administration Increases Retinal Docosahexaenoic Acid and Neuroprotectin D1 in a Murine Model of Retinopathy of Prematurity.
Investigative ophthalmology & visual science, 2018Co-Authors: Lynn C Shaw, Sergio Li Calzi, Leni Moldovan, Nilanjana Sengupta-caballero, Judith Quigley, Mircea Ivan, Bokkyoo Jun, Nicolas G. Bazan, Michael E. BoultonAbstract:Purpose Low levels of the long chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) have been implicated in retinopathy of prematurity (ROP). However, oral DHA suffers from poor palatability and is associated with increased bleeding in premature infants. We asked whether oral administration of the neutraceutical arginine-glutamine (Arg-Glu) could increase retinal DHA and improve outcomes in a mouse model of oxygen-induced retinopathy (OIR). Methods Postnatal day 7 (P7) pups were maintained at 75% oxygen for 5 days and then returned to room air on P12. Pups were gavaged twice daily with Arg-Gln or vehicle from P12 to P17 and eyes were harvested for analysis on P17. Vaso-obliteration and vascular density were assessed on retinal flat mounts and preretinal neovascularization was assessed on retinal cross sections. Retinas were used for measurement of DHA and 10,17S-docosatriene (neuroprotectin D1, NPD1), a key DHA-derived lipid, and for analysis by reverse-phase protein array (RPPA). Results With Arg-Gln treatment, retinal DHA and NPD1 levels were increased in OIR pups. Arg-Gln reduced preretinal neovascularization by 39 ± 6% (P < 0.05) relative to vehicle control. This was accompanied by a restoration of vascular density of the retina in the pups treated with Arg-Gln (73.0 ± 3.0%) compared to vehicle (53.1 ± 3.4%; P < 0.05). Arg-Gln dipeptide restored OIR-induced signaling changes toward normoxia and was associated with normalization of insulin-like growth factor receptor 1 signaling and reduction of apoptosis and an increase in anti-apoptosis proteins. Conclusions Arg-Gln may serve as a safer and easily tolerated nutraceutical agent for prevention or treatment of ROP.
-
Arginyl-glutamine dipeptide or docosahexaenoic acid attenuate hyperoxia-induced lung injury in neonatal mice
Nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Abstract Objectives Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates. However, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA, a long-chain ω-3 fatty acid with anti-inflammatory properties, to exert benefits on hyperoxia-induced lung injury has not to our knowledge been investigated. The aim of this study was to investigate whether Arg-Gln dipeptide or DHA could attenuate markers of injury and inflammation in neonatal mouse lungs exposed to hyperoxia. Methods Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 d. After 5 d of hyperoxic exposure (postnatal days 7–12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 d (postnatal days 12–17). Mouse pups received Arg-Gln (5 g · kg −1 · d −1 ) or DHA (5 g · kg −1 · d −1 ) or saline orally from postnatal days 12 through 17. Histologic changes, myeloperoxidase, lactate dehydrogenase, inflammatory cytokines, and nuclear factor-κB inhibitor levels were checked in each group. Results The Arg-Gln and DHA prevented the development of key markers of injury, including histologic changes, myeloperoxidase, lactate dehydrogenase, and inflammatory cytokines interleukin-6 and C-X-C motif ligand 1 (CXCL1)/keratinocyte-derived chemokine (KC). The highly beneficial effects of Arg-Gln on the reversal of oxygen-induced lung damage was associated with restoration of levels of nuclear factor-κB inhibitor. Conclusion The Arg-Gln and DHA, with protective effects on hyperoxic lung injury in neonatal mice, are promising nutritional adjuncts that may prevent lung damage owing to oxygen toxicity in infants.
-
Arginyl-Glutamine Dipeptide or Docosahexaenoic Acid Attenuates Hyperoxia-induced Small Intestinal Injury in Neonatal Mice
Journal of pediatric gastroenterology and nutrition, 2012Co-Authors: Xueyan Liu, Lynn C Shaw, Maria B. Grant, Sergio Li Calzi, Josef NeuAbstract:Background and Objective Supplementation studies of glutamine, argi-nine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model.
-
The dipeptide Arg-Gln inhibits retinal neovascularization in the mouse model of oxygen-induced retinopathy.
Investigative ophthalmology & visual science, 2006Co-Authors: Josef Neu, Lynn C Shaw, Aqeela Afzal, Hao Pan, Esteban Gallego, Sergio Li Calzi, Sergio Caballero, P.e. Spoerri, Maria B. GrantAbstract:PURPOSE. Premature infants undergoing intensive care are highly vulnerable to amino acid deprivation. Supplementation of glutamine or arginine has resulted in beneficial effects in human neonates. This study was conducted to examine the effect of the dipeptide arginyl-glutamine (Arg-Gln) on vascular endothelial cell growth factor (VEGF) levels in primary human retinal pigment epithelial (hRPE) cell cultures and on inhibition of neovascularization in the oxygen-induced retinopathy (OIR) model. METHODS. The effects of Arg-Gln on VEGF levels were measured in supernates from hRPE cells by using ELISAs. For in vivo studies, mouse pups received twice-daily intraperitoneal injections of Arg-Gln, a control dipeptide (Ala-Gly) or were not injected. Retinal flatmounts from one cohort were prepared and retinal vessel morphology examined. The contralateral eyes were embedded, sectioned, and stained to count preretinal neovascular nuclei. RNA was isolated from retinas of selected animals and was used to quantify VEGF mRNA by realtime RT-PCR. RESULTS. Treatment of hRPE cells with Arg-Gln decreased VEGF levels in a dose-dependent manner. In the OIR model, Arg-Gln at 5 g/kg per day reduced preretinal neovascularization by 82% 7% (P 0.005), when compared with the control dipeptide Ala-Gly, and reduced VEGF mRNA by 64% 9% (P 0.001). CONCLUSIONS. Arg-Gln dramatically inhibited retinal neovascularization in the OIR model. This effect was associated with a reduction in retinal VEGF mRNA levels. Similarly the dipeptide reduced VEGF expression in hRPE cells, a cell type likely to respond to retinal hypoxia by expressing VEGF. Arg-Gln appears to be safe and, with future studies in human infants, may prove beneficial in the prevention of ROP. (Invest Ophthalmol
