Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pr...Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.展开更多
Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/intervent...Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.展开更多
BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammat...BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.展开更多
Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking G...Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking Gpx1 cDNA, Klk1 cDNA, and Ksp-cadherin BAC as templates. After being testified, the PCR products were inserted into the expressive vector pIRES-EGFP step-by-step to produce a recombinant vector Ksp-cadherin-Gpx1-Klk1. This vector was examined by restriction enzyme digestion and sequence analysis. Results The recombinant expressive vector Ksp-cadherin-Gpx1-Klk1 was successfully constructed. Conclusion The construction of the recombinant vector Ksp-cadherin-Gpx1-Klk1 laid foundations for investigations in establishing transgenic animal models, the over-expression of Gpx1 and Klk1 in mammal kidney, and gene therapy for ischemia-reperfusion injury during kidney transplantation.展开更多
Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2...Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) iS endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. Methods The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were ,detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine i^-synthase, cystathionine y-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer. Results H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06+0.43) nmol/mg; H2S production: (0.17+0.06) nmol.minl.mgl). Gene and protein expressions of the three H2S producing enzymes ~vere detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P 〈0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P 〈0.01). Conclusion H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.展开更多
Objective: To observe the myocardial protecting effects of Ginaton (Ginkgo biloba extract) on ischemic-reperfusion injured myocardium during cardiopulmonary bypass (CPB). Methods: Twenty patients selected undergoing m...Objective: To observe the myocardial protecting effects of Ginaton (Ginkgo biloba extract) on ischemic-reperfusion injured myocardium during cardiopulmonary bypass (CPB). Methods: Twenty patients selected undergoing mitral valvular replacement were randomly divided into two groups. Control group: 10 patients, intermittent intra-aortic infusion with cold St.Thomas solution during hypothermic CPB. Ginaton group: 10 patients, intermittent intra-aortic infusion with cold St. Thomas solution containing Ginaton (0.5 mg·kg -1). Changes of ultrastructure levels of adenosine triphosphate (ATP), malondialdehyde (MDA) and hemodynamic data were measured. Results: Hemodynamic parameters in the Ginaton group were maintained better than those in the control group. MDA in the control group was significantly elevated during ischemic-reperfusion (P<0.05), while in the Ginaton group, there were no obvious change. The levels of ATP and energy change in the Ginaton group were obviously higher than those in the control group at declamping aorta (P<0.05). The percentage of normal mitochondria and glycogen content were significantly higher in the Ginaton group than that in the control group at declamping aorta (P<0.05). Conclusion: Ginkgo biloba extract may provide a beneficial effect on myocardial protection in ultrastructural preservation, prevention of high energy phosphate depletion, reduction in free radicals production and improvement of myocardial function.展开更多
Objective: To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium, on mouse model of cerebral ischemia-reperfusion (I/R) in vivo. Methods: ICR mice were subject...Objective: To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium, on mouse model of cerebral ischemia-reperfusion (I/R) in vivo. Methods: ICR mice were subjected to an I h transient middle cerebral artery occlusion (MCAO) and fol- lowed by 24 h of reperfusion. Neurological deficits, infarct volume, brain edema and survive rate were measured, respectively. The levels of brain IL-1β, TNF-a, ROS and DNA-binding activity of NF-KB p65 were measured by ELISA kits. The levels of malondialdehyde (MDA) and activities of superoxide dismu- tase (SOD) were detected by spectrophotometry, and the release of nitric oxide (NO) were detected by Griess kit. Results: ICT markedly reduced the neurological deficit scores, brain edema, infarct volume and increased the survival rate of the cerebral I/R mice. The expression of IL-Iβ, TNF-α, NO, MDA and DNA-binding activity of NF-KB p65 were significantly inhibited by ICT, while the activity of SOD were up-regulated at the same time. Conclusion: ICT possessed significant neuroprotective effects in cerebral I/R mice, which might be related to prevent neuroinflammatory and oxidative damage.展开更多
文摘Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.
基金supported by the Early Career Scheme(ECS)2022/23(CUHK 24110822)from the Research Grants Council of Hong Kongthe Direct Grant for Research 2020/21(2020.035)+3 种基金Project Impact Enhancement Fund(PIEF)(PIEF/Ph2/COVID/08)Improvement on Competitiveness in Hiring New Faculties Funding Scheme from CUHK as well as the Centre for Cardiovascular Genomics and Medicine(CCGM)of the Lui Che Woo Institute of Innovative Medicine CUHK(to S.B.O.)a CUHK Department of Medicine&Therapeutics(MEDT)-funded PhD studenta CUHK Vice-Chancellor’s PhD Scholarship holder。
文摘Large animal models of cardiac ischemia-reperfusion are critical for evaluation of the efficacy of cardioprotective interventions prior to clinical translation.Nonetheless,current cardioprotective strategies/interventions formulated in preclinical cardiovascular research are often limited to small animal models,which are not transferable or reproducible in large animal models due to different factors such as:(i)complex and varied features of human ischemic cardiac disease(ICD),which are challenging to mimic in animal models,(ii)significant differences in surgical techniques applied,and(iii)differences in cardiovascular anatomy and physiology between small versus large animals.This article highlights the advantages and disadvantages of different large animal models of preclinical cardiac ischemic reperfusion injury(IRI),as well as the different methods used to induce and assess IRI,and the obstacles faced in using large animals for translational research in the settings of cardiac IR.
文摘BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.
基金supported by the National Natural Science Foundation of China (No.30471640)
文摘Objective To construct and identify the Gpx1-Klk1 vector which contains kidney-specific promoter (Ksp-cadherin). Methods Through PCR amplification, the human Gpx1, Klk1, and Ksp-cadherin cDNA were obtained by taking Gpx1 cDNA, Klk1 cDNA, and Ksp-cadherin BAC as templates. After being testified, the PCR products were inserted into the expressive vector pIRES-EGFP step-by-step to produce a recombinant vector Ksp-cadherin-Gpx1-Klk1. This vector was examined by restriction enzyme digestion and sequence analysis. Results The recombinant expressive vector Ksp-cadherin-Gpx1-Klk1 was successfully constructed. Conclusion The construction of the recombinant vector Ksp-cadherin-Gpx1-Klk1 laid foundations for investigations in establishing transgenic animal models, the over-expression of Gpx1 and Klk1 in mammal kidney, and gene therapy for ischemia-reperfusion injury during kidney transplantation.
基金The study was supported by the grants from Major Basic Research Development Program of People's Republic of China (No. 2011CB503904 and No. 2013CB933801) and National Natural Science Foundation of China (No. 81070212).
文摘Background Skeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) iS endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle. Methods The study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were ,detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine i^-synthase, cystathionine y-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer. Results H2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06+0.43) nmol/mg; H2S production: (0.17+0.06) nmol.minl.mgl). Gene and protein expressions of the three H2S producing enzymes ~vere detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P 〈0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P 〈0.01). Conclusion H2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.
文摘Objective: To observe the myocardial protecting effects of Ginaton (Ginkgo biloba extract) on ischemic-reperfusion injured myocardium during cardiopulmonary bypass (CPB). Methods: Twenty patients selected undergoing mitral valvular replacement were randomly divided into two groups. Control group: 10 patients, intermittent intra-aortic infusion with cold St.Thomas solution during hypothermic CPB. Ginaton group: 10 patients, intermittent intra-aortic infusion with cold St. Thomas solution containing Ginaton (0.5 mg·kg -1). Changes of ultrastructure levels of adenosine triphosphate (ATP), malondialdehyde (MDA) and hemodynamic data were measured. Results: Hemodynamic parameters in the Ginaton group were maintained better than those in the control group. MDA in the control group was significantly elevated during ischemic-reperfusion (P<0.05), while in the Ginaton group, there were no obvious change. The levels of ATP and energy change in the Ginaton group were obviously higher than those in the control group at declamping aorta (P<0.05). The percentage of normal mitochondria and glycogen content were significantly higher in the Ginaton group than that in the control group at declamping aorta (P<0.05). Conclusion: Ginkgo biloba extract may provide a beneficial effect on myocardial protection in ultrastructural preservation, prevention of high energy phosphate depletion, reduction in free radicals production and improvement of myocardial function.
基金financially supported by the Natural Foundation of Shandong Province (ZR2015QL002)
文摘Objective: To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium, on mouse model of cerebral ischemia-reperfusion (I/R) in vivo. Methods: ICR mice were subjected to an I h transient middle cerebral artery occlusion (MCAO) and fol- lowed by 24 h of reperfusion. Neurological deficits, infarct volume, brain edema and survive rate were measured, respectively. The levels of brain IL-1β, TNF-a, ROS and DNA-binding activity of NF-KB p65 were measured by ELISA kits. The levels of malondialdehyde (MDA) and activities of superoxide dismu- tase (SOD) were detected by spectrophotometry, and the release of nitric oxide (NO) were detected by Griess kit. Results: ICT markedly reduced the neurological deficit scores, brain edema, infarct volume and increased the survival rate of the cerebral I/R mice. The expression of IL-Iβ, TNF-α, NO, MDA and DNA-binding activity of NF-KB p65 were significantly inhibited by ICT, while the activity of SOD were up-regulated at the same time. Conclusion: ICT possessed significant neuroprotective effects in cerebral I/R mice, which might be related to prevent neuroinflammatory and oxidative damage.