Hepatic ischemia-reperfusion injury (IRI) is a pathophysiological event post liver surgery or transplantation and significantly influences the prognosis of liver function. The mechanisms of IRI remain unclear, and effective methods are lacking for the prevention and therapy of IRI. Several factors/pathways have been implicated in the hepatic IRI process, including anaerobic metabolism, mitochondria, oxidative stress, intracellular calcium overload, liver Kupffer cells and neutrophils, and cytokines and chemokines. The role of nitric oxide (NO) in protecting against liver IRI has recently been reported. NO has been found to attenuate liver IRI through various mechanisms including reducing hepatocellular apoptosis, decreasing oxidative stress and leukocyte adhesion, increasing microcirculatory flow, and enhancing mitochondrial function. The purpose of this review is to provide insights into the mechanisms of liver IRI, indicating the potential protective factors/pathways that may help to improve therapeutic regimens for controlling hepatic IRI during liver surgery, and the potential therapeutic role of NO in liver IRI.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Liver; Ischemia-reperfusion injury; Cytokine; Chemokine; Kupffer cells; Mitochondria; Nitric oxide Core tip: This review provides insights into several key mechanisms of liver ischemia-reperfusion injury, including the effects of anaerobic metabolism and the role of mitochondria, oxidative stress, intracellular calcium overload, liver Kupffer cells and neutrophils, and cytokines and chemokines; and summarizes the protective effects of nitric oxide.Guan LY, Fu PY, Li PD, Li ZN, Liu HY, Xin MG, Li W. Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

This study aimed to compare the plasma levels of angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), kallikrein (KLK1) and interleukin-6 (IL-6) in ST segment elevation myocardial infarction (STEMI) patients with different ACE Insertion/deletion (I/D) polymorphisms in a Chinese population. The ACE genotypes were determined in the 199 STEMI patients and 216 control subjects. STEMI patients were divided into three groups based on the ACE genotypes. Single polymerase chain reaction (PCR) was performed to characterize ACE I/D polymorphisms. Plasma levels of ACE, AngII, KLK1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). We found that the DD or ID genotype was significantly independently associated with high ACE (OR = 4.697; 95% CI = 1.927–11.339), KLK1 (3.339; 1.383–8.063) and IL-6 levels (OR = 2.10; 1.025–4.327) in STEMI patients. However, there was no statistical significance between the ACE I/D polymorphism and AngII plasma levels whether in univariate or multivariate logistic regression. Additionally, we detected a significantly positive correlation between plasma KLK1 levels and IL-6 levels in STEMI patients (r = 0.584, P < 0.001). The study showed high levels of ACE, KLK1 and IL-6 were detected when the D allele was present, but AngII plasma levels was not influenced by the ACE I/D polymorphism.