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Zhou W.,Tianjin University | Zhao L.,Tianjin University | Wang J.,Tianjin University | Li S.,Chinese Academy of Sciences | And 7 more authors.
Artificial Cells, Nanomedicine and Biotechnology | Year: 2013

Objectives: To reduce the mean molecular weight and to increase the effective polymerization ratio (REff) of polymerized human placenta hemoglobin (PolyPHb). Methods: Three factors of GDA-PolyPHb process such as the approach of feeding GDA (FGDA), hemoglobin concentration ([Hb]) and the molar ratio of GDA, and hemoglobin(RGDA:Hb) were investigated. Finally, the expansion experiments were conducted with optimal conditions. Results: The data showed that the HBOCs with the REff of 67.35% and lower of 162.70 kDa were prepared by optimal conditions. Conclusion: Compared to original process, the optimal process greatly decreased the and increased the REff. Copyright © 2013 Informa Healthcare USA, Inc.


Wei L.,Surgery Academy | Wu R.-B.,Surgery Academy | Yang C.-M.,Institute of Tianjin Union Biotechnology Development | Zheng S.-Y.,Surgery Academy | Yu X.-Y.,Guangdong Academy of Medical science
Cardiology | Year: 2011

Objectives: The etiology of myocardial ischemia/reperfusion (I/R) injury is multifactorial, but activation of the innate immune system and the resulting inflammatory response are important components of I/R injury. The aim of this study was to investigate the protective effect of a hemoglobin-based oxygen carrier (HBOC) on cold I/R heart and to explore the underlying mechanisms. Methods: Isolated Sprague-Dawley rat hearts were perfused in the Langendorff mode. After 30 min of basal perfusion, rat hearts were arrested with histidine-tryptophan-ketoglutarate solution (HTKs) with or without an HBOC and hypothermically stored (4°C) for 9 or 14 h, followed by 2 h of reperfusion. Results: Compared with HTKs alone, the HBOC in HTKs greatly improved heart contraction and decreased infarct size, necrosis and apoptosis, which was related to the reduced expression of Toll-like receptor 2 (TLR 2), TLR 4, TNF-α, IL-1β and nuclear factor-κB (NF-κB) activation. Conclusions: Our results demonstrated that the HBOC protected isolated rat heart from cold I/R injury and this protection was associated with attenuation of the expression of the TLR 2 and TLR 4/NF-κB signaling pathway, which may down-regulate the inflammatory response. Copyright © 2011 S. Karger AG, Basel.


Zhao L.,Tianjin University | Li S.,Chinese Academy of Sciences | Li F.,Institute of Tianjin Union Biotechnology Development | Wang J.,Tianjin University | Yang C.,Chinese Academy of Sciences
Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi | Year: 2013

The present study was aimed to investigate the influence of freeze-drying on the quality of polymerized human placenta hemoglobin (PolyPHb). The PolyPHb solution was freeze-drying under suitable conditions. Hemoglobin concentration, methemoglobin (MetHb) content, UV spectrum, Fe3 content, oxygen-carrying capacity, pH, the average molecular weight and its distribution, circular dichroism, oxygen equilibrium curve and other indicators were measured before and after freeze-drying. The appearance, residual water content, rehydration time of the lyophilized product were also evaluated. The results showed that there was no significant difference on all the indicators measured above, which indicated that freeze-drying process had no effect on the physical and chemical properties of PolyPHb, as well as on its biological activity. Therefore, the properties of PolyPHb were stable during this freeze-drying process and could be preserved after such freeze-drying process.


Zhao L.,Tianjin University | Zhou W.,Tianjin University | Wang J.,Tianjin University | Li S.,Chinese Academy of Sciences | And 4 more authors.
Artificial Cells, Nanomedicine and Biotechnology | Year: 2014

In this study, lyophilization was applied to polymerized human placenta hemoglobin (PolyPHb) solution. The lyophilization process was carried out with freezing at - 70°C for 5 h and two phases of drying: the first phase of drying was carried out at -35°C-35°C for 16 h and the second phase at 35°C for 8 h. Hemoglobin (Hb) concentration, methemoglobin (MetHb) content, oxygen-carrying capacity, Fe3+ content, pH, UV spectrum, average molecular weight and its distribution, circular dichroism, SDS-PAGE, P 50, crystal osmotic pressure, colloid osmotic pressure, zeta potential, average particle size, and other indicators were measured before and after lyophilization. Residual water content and rehydration time of the lyophilized products were also evaluated. All the indicators of lyophilized samples showed that the physical and biochemical properties of PolyPHb are not markedly changed before and after lyophilization. In this light, lyophilization may be a promising method for the preservation of PolyPHb solution. © 2014 Informa Healthcare USA, Inc.


Wei L.,Surgery Academy | Wu R.B.,Surgery Academy | Yang C.M.,Institute of Tianjin Union Biotechnology Development | Zheng S.-Y.,Guangdong Academy of Medical science | Yu X.-Y.,Surgery Academy
Microvascular Research | Year: 2011

Ischaemia/reperfusion (I/R) injury is harmful to the cardiovascular system and is responsible for the inflammatory response, which, in turn, aggravates cardiac dysfunction. This study was designed to investigate the protective effect and potential mechanism of a haemoglobin-based oxygen carrier on cold I/R-injured hearts. Isolated Sprague-Dawley rat hearts were perfused in Langendorff mode. After a 30-min basal perfusion, rat hearts were arrested and hypothermically stored at 4 °C for 12. h followed by a 2-h reperfusion. Compared with histidine-tryptophan-ketoglutarate solution (HTKs), polymerised placenta haemoglobin (PolyPHb) in HTKs greatly improved heart contraction and decreased infarction size, necrosis, and apoptosis, which was related to reduced expression of TLR2, TLR4, TNF-α, and IL-1β, and NF-κB activation. Our results demonstrate the cardioprotective effect of PolyPHb on cold I/R-injured hearts and revealed that this protection was mediated in large part by attenuation of TLR2 and -4/NF-κB signalling pathway and could possibly down-regulate the inflammatory response. © 2011 Elsevier Inc.


Li T.,University of Sichuan | Liu J.,University of Sichuan | Yang C.,Institute of Tianjin Union Biotechnology Development
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2010

This study was designed to investigate whether polymerized human placenta hemoglobin (PolyPHb) pretreatment provided protection to the heart after ischemia/reperfusion (I/R) injury. After 10-min basal perfusion, isolated Sprague-Dawley rat hearts were pretreated with 0.1 gHb/dL PolyPHb and subjected to I/R injury. PolyPHb pretreatment greatly reduced the decreases in left ventricular developed pressure (LVDP), maximum LVDP increase and decrease rate (±dp/dt), and the increase in left ventricular end-diastolic pressure (LVEDP) as compared to the control group. Moreover, the myocardial infarction and troponin-I release were significantly reduced in the pre-HBOCs group. Therefore, PolyPHb pretreatment was protective to the isolated I/R heart. © 2010 Informa UK Ltd.


Wu W.,University of Sichuan | Li T.,University of Sichuan | Liu J.,University of Sichuan | Yang C.,Institute of Tianjin Union Biotechnology Development
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

This study was designed to investigate the influence of polymerized human placenta hemoglobin (PolyPHb) pretreatment on ischemia/reperfusion (I/R) injury-induced myocardial apoptosis. Isolated Sprague-Dawley rat hearts were perfused by Langendorff model. After basal perfusion, hearts were arrested by St.Thomas' solution (STS) with (Pre-HBOC group) or without PolyPHb (STS group), then subjected to I/R injury. Our results showed that PolyPHb pretreatment greatly reduced the TUNEL-positive myocardial cells and decreased the caspase-3 activity and cleavage, which was further confirmed by the linear regression analysis. Therefore, PolyPHb pretreatment was beneficial to attenuation of myocardial apoptosis and provided protection to the heart against I/R injury. © 2011 Informa Healthcare USA, Inc.


You Z.,University of Sichuan | Li T.,University of Sichuan | Yang C.,Institute of Tianjin Union Biotechnology Development | Wu H.,University of Sichuan | Zeng Y.,University of Sichuan
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

This study was designed to compare the influence of deoxygenated hemoglobin-based oxygen carrier (HBOC) pretreatment and ischemia preconditioning on cardiac ischemia/reperfusion (I/R) injury. Langendorff-perfused rat hearts were pretreated with 0.1 gHb/dL deoxygenated HBOC or ischemia, then subjected to 50-min warm ischemia and 2-hr reperfusion. The results indicated that deoxygenated HBOC pretreatment and ischemia preconditioning both equally improved the recovery of cardiac function, and reduced the cardiac enzyme release and myocardial histopathological changes as compared to the control group. Therefore our study demonstrated that deoxygenated HBOC pretreatment and ischemia precondition provided equivalent protection to the isolated heart against I/R injury. © 2011 Informa Healthcare USA, Inc.


Li T.,University of Sichuan | Zhou R.,University of Sichuan | Xiang X.,University of Sichuan | Zhu D.,University of Sichuan | And 4 more authors.
Artificial Cells, Blood Substitutes, and Biotechnology | Year: 2011

This study was to investigate whether polymerized human placenta hemoglobin (PolyPHb) given before ischemia protects in vivo rat heart function against ischemia/reperfusion (I/R) injury. Forty-five male Sprague-Dawley rats were randomly divided (n = 15 per group) into a sham group, control group (pretreatment with Lactated Ringer's solution), or PolyPHb group (pretreatment with 0.1gHb/kg PolyPHb). Rat hearts were subjected to 30-min ischemia by occlusion of left anterior descending, followed by 2-hr reperfusion. As compared to the control group, PolyPHb preserved cardiac function and reduced cardiac troponin-I release and histopathological changes. Therefore, PolyPHb pretreatment provided a profound cardioprotective effect on the in vivo rat heart. © 2011 Informa Healthcare USA, Inc.

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