Continuous Monitoring of Serum Tumor Necrosis Factor-α for Patients with TEMIS Treated by Nitrates Postconditioning during PCI

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.

Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

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 mitigated hepatic IRI in mice,as evidenced by the decreased ALT and reduced injury on histology.These results have potential implications on mitigating IRI during liver transplantation and resection.

Leukocyte cell-derived chemotaxin 2(LECT2)regulates liver ischemia-reperfusion injury

Background and aim Hepatic ischemia–reperfusion injury(IRI)is a significant challenge in liver transplantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors.Materials and methods This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.Results Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating therapeutic potential.Conclusions Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Protective effect of indomethacin in renal ischemia-reperfusion injury in mice

Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.

Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation

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.