Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of is...Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 miti展开更多
Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patie...Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patients with STEMI who underwent PCI were selected, except for obvious anemia, head trauma, cerebral hemorrhage, hypotension (systolic blood pressure less than 90 mmHg), and patients with autoimmune diseases, all kinds of acute and chronic infections and malignant tumors. They were randomly divided into PCI standardized treatment group and isosorbide dinitrate postconditioning during PCI group. The concentrations of cTnI and TNF-α in serum were detected by ELISA method in each group before PCI and after 2 hours, 1 day, 4 days and 7 days of PCI. Results: 1) There were no statistically significant differences in sex, age, smoking history, diabetes, hypertension and blood lipid abnormality in two groups. 2) Before operation, the concentration of cTnI in two groups was not statistically significant. The concentration of cTnI in the experimental group was lower than that of the control group after 4 days and 7 days of PCI, and P α in two groups before operation. The concentration of TNF-α in the experimental group was lower than that in the control group after 1 day, 4 days and 7 days of PCI, and P α in two groups was both in 1 day after operation, and the peak level of the experimental group and the level of each time after the operation were lower than that of the control group. Conclusion: Nitrates postconditioning during PCI in patients with STEMI has a protective effect on myocardial ischemia-reperfusion injury. Nitrates postconditioning has an effect to reduce the level of TNF-α of patients with STEMI after PCI treatment, and may have the mechanism of alleviating the inflammatory response after myocardial ischemia and reperfusion.展开更多
Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protecti...Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.展开更多
Acute renal failure has a 50% - 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of...Acute renal failure has a 50% - 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of laser application to stem cells in the bone marrow, on the kidneys of rats that had undergone ischemia-reperfusion injury (IRI). IRI was induced by occlusion of the renal artery to 3- and 7-month-old rats for 15 or 30 minutes. In an additional experiment IRI was applied to both kidneys for 20 min each in 2-3-month-old rats. Rats were then divided randomly into two groups of control and laser-treated. Laser therapy (Ga-Al-As 810 nm, 200 mW output for 2 min) was applied to the bone marrow 1 and 7 days post-IRI to the kidneys, and rats were sacrificed 2 weeks later. Histomorphometry and immunohistochemistry were performed on kidney sections and blood markers for kidney function. Quantitative histomorphometric analysis revealed a reduction in dilatation of the renal tubules, restored structural integrity of the renal tubules, and reduced necrosis in the laser-treated rats as compared to the control, non-laser-irradiated group. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p = 0.015) 3.2-fold higher compared to the control group. Creatinine and blood urea nitrogen content were significantly lower in the laser-treated rats as compared to control. It is concluded that LLLT application to the bone marrow (BM) causes a significant increase in the density of mesenchymal stem cells in the kidneys post-IRI, probably by induction of stem cells in the BM, which subsequently migrate to the IRI kidney, significantly reducing the pathological features of the kidney and increasing kidney function post IRI.展开更多
文摘Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 miti
文摘Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patients with STEMI who underwent PCI were selected, except for obvious anemia, head trauma, cerebral hemorrhage, hypotension (systolic blood pressure less than 90 mmHg), and patients with autoimmune diseases, all kinds of acute and chronic infections and malignant tumors. They were randomly divided into PCI standardized treatment group and isosorbide dinitrate postconditioning during PCI group. The concentrations of cTnI and TNF-α in serum were detected by ELISA method in each group before PCI and after 2 hours, 1 day, 4 days and 7 days of PCI. Results: 1) There were no statistically significant differences in sex, age, smoking history, diabetes, hypertension and blood lipid abnormality in two groups. 2) Before operation, the concentration of cTnI in two groups was not statistically significant. The concentration of cTnI in the experimental group was lower than that of the control group after 4 days and 7 days of PCI, and P α in two groups before operation. The concentration of TNF-α in the experimental group was lower than that in the control group after 1 day, 4 days and 7 days of PCI, and P α in two groups was both in 1 day after operation, and the peak level of the experimental group and the level of each time after the operation were lower than that of the control group. Conclusion: Nitrates postconditioning during PCI in patients with STEMI has a protective effect on myocardial ischemia-reperfusion injury. Nitrates postconditioning has an effect to reduce the level of TNF-α of patients with STEMI after PCI treatment, and may have the mechanism of alleviating the inflammatory response after myocardial ischemia and reperfusion.
基金supported by Public Projects of Zhejiang Province(No.LGF21H030006)Major Science and Technology Projects of Hainan Province(No.ZDKJ2019009)+2 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LZ21H180001)a Research Project of Jinan Microecological Biomedicine Shandong Laboratory(Nos.JNL-2022002A,JNL-2022007B,and JNL-2022023C)the National Natural Science Foundation of China(No.82000618).
文摘Liver transplantation(LT),an ultimate and vital method for treating end-stage liver disease,is often accompanied by ischemiareperfusion injury(IRI)resulting from warm or cold ischemia of the donor liver.Organ protection techniques are used to improve the quality of liver grafts(from retrieval to implantation).Reactive oxygen species(ROS)cause oxidative stress,which is considered a crucial factor in IRI after LT.Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues.In this study,we synthesized ceria nanoparticles(NPs)with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibility in vivo.We investigated the potential organprotective effect of ceria NPs and the underlying mechanisms.Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver grafts in vivo.The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusion ex vivo.Ceria NPs attenuated hypoxia reoxygenation-or H_(2)O_(2)-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavenging in vitro.These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap1)/heme oxygenase 1(HO-1)signaling pathway.In conclusion,ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.
文摘Acute renal failure has a 50% - 80% mortality rate. Currently, treatment options for this life-threatening disease are limited. Low-level laser therapy (LLLT) has been found to modulate biological activity. The aim of the present study was to investigate the possible beneficial effects of laser application to stem cells in the bone marrow, on the kidneys of rats that had undergone ischemia-reperfusion injury (IRI). IRI was induced by occlusion of the renal artery to 3- and 7-month-old rats for 15 or 30 minutes. In an additional experiment IRI was applied to both kidneys for 20 min each in 2-3-month-old rats. Rats were then divided randomly into two groups of control and laser-treated. Laser therapy (Ga-Al-As 810 nm, 200 mW output for 2 min) was applied to the bone marrow 1 and 7 days post-IRI to the kidneys, and rats were sacrificed 2 weeks later. Histomorphometry and immunohistochemistry were performed on kidney sections and blood markers for kidney function. Quantitative histomorphometric analysis revealed a reduction in dilatation of the renal tubules, restored structural integrity of the renal tubules, and reduced necrosis in the laser-treated rats as compared to the control, non-laser-irradiated group. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p = 0.015) 3.2-fold higher compared to the control group. Creatinine and blood urea nitrogen content were significantly lower in the laser-treated rats as compared to control. It is concluded that LLLT application to the bone marrow (BM) causes a significant increase in the density of mesenchymal stem cells in the kidneys post-IRI, probably by induction of stem cells in the BM, which subsequently migrate to the IRI kidney, significantly reducing the pathological features of the kidney and increasing kidney function post IRI.
