Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality. In the clinical setting, it was once believed that myocardial dysfunction was not a major pathological process in the septic patients, at least in part, due to the unavailability of suitable clinical markers to assess intrinsic myocardial function during sepsis. Although sepsis-induced myocardial dysfunction has been studied in clinical and basic research for more than 30 years, its pathophysiology is not completely understood, and no specific therapies for this disorder exist. The purpose of this review is to summarize our current knowledge of sepsis-induced myocardial dysfunction with a special focus on pathogenesis and clinical characteristics.

Cardiomyocyte apoptosis is an important event in doxorubicin (DOX)-induced cardiac injury. The aim of the present study was to investigate the protection of berberine (Ber) against DOX- triggered cardiomyocyte apoptosis in neonatal rat cardiomyocytes and rats. In neonatal rat cardiomyocytes, Ber attenuated DOX-induced cellular injury and apoptosis in a dose-dependent manner. However, Ber has no significant effect on viability of MCF-7 breast cancer cells treated with DOX. Ber reduced caspase-3 and caspase-9, but not caspase-8 activity in DOX-treated cardiomyocytes. Furthermore, Ber decreased adenosine monophosphate-activated protein kinase α (AMPKα) and p53 phosphorylation at 2 h, cytosolic cytochrome c and mitochondrial Bax levels and increased Bcl-2 level at 6 h in DOX-stimulated cardiomyocytes. Pretreatment with compound C, an AMPK inhibitor, also suppressed p53 phosphorylation and apoptosis in DOX-treated cardiomyocytes. DOX stimulation for 30 min led to a loss of mitochondrial membrane potential and a rise in the AMP/ATP ratio. Ber markedly reduced DOX-induced mitochondrial membrane potential loss and an increase in the AMP/ATP ratio at 1 h and 2 h post DOX exposure. In in vivo experiments, Ber significantly improved survival, increased stroke volume and attenuated myocardial injury in DOX-challenged rats. TUNEL and Western blot assays showed that Ber not only decreased myocardial apoptosis, caspase-3 activation, AMPKα and p53 phosphorylation, but also increased Bcl-2 expression in myocardium of rats exposed to DOX for 84 h. These findings indicate that Ber attenuates DOX-induced cardiomyocyte apoptosis via protecting mitochondria, inhibiting an increase in the AMP/ATP ratio and AMPKα phosphorylation as well as elevating Bcl-2 expression, which offer a novel mechanism responsible for protection of Ber against DOX-induced cardiomyopathy.

dInfluenza A virus NS2 protein, also called nuclear export protein (NEP), is crucial for the nuclear export of viral ribonucleoproteins. However, the molecular mechanisms of NEP mediation in this process remain incompletely understood. A leucine-rich nuclear export signal (NES2) in NEP, located at the predicted N2 helix of the N-terminal domain, was identified in the present study. NES2 was demonstrated to be a transferable NES, with its nuclear export activity depending on the nuclear export receptor chromosome region maintenance 1 (CRM1)-mediated pathway. The interaction between NEP and CRM1 is coordinately regulated by both the previously reported NES (NES1) and now the new NES2. Deletion of the NES1 enhances the interaction between NEP and CRM1, and deletion of the NES1 and NES2 motifs completely abolishes this interaction. Moreover, NES2 interacts with CRM1 in the mammalian two-hybrid system. Mutant viruses containing NES2 alterations generated by reversed genetics exhibit reduced viral growth and delay in the nuclear export of viral ribonucleoproteins (vRNPs). The NES2 motif is highly conserved in the influenza A and B viruses. The results demonstrate that leucine-rich NES2 is involved in the nuclear export of vRNPs and contributes to the understanding of nucleocytoplasmic transport of influenza virus vRNPs.T he transport of macromolecules between the nucleus and the cytoplasm is mediated by nuclear pore complexes (NPCs) embedded in the nuclear envelope. Small molecules can pass through NPCs via passive diffusion, whereas the translocation of larger molecules (Ͼ50 kDa) generally requires specific transport receptors (1). Exportins are a group of transport receptors responsible for the nuclear export of cargo molecules. Chromosome region maintenance 1 (CRM1; also called exportin1/Xpo1) has been identified as an export factor for the leucine-rich nuclear export signal (NES) and plays an important role in the nuclear export of leucine-rich NES-containing proteins (2-4). Cellular CRM1-mediated nuclear export can be specifically inhibited by the nuclear export inhibitor leptomycin B (LMB) (5, 6).The genome of influenza A virus contains eight single-stranded RNA segments packed into viral ribonucleoprotein (vRNP) complexes (7). Unlike most RNA viruses replicated in the cytoplasm, influenza virus is rare in that it replicates in the nucleus. The newly synthesized progeny vRNP complex, which consists of the negative-strand viral RNA (vRNA), the trimeric polymerase complex of PB1-PB2-PA, and the nucleoprotein (NP) in the nucleus, requires export to the assembly site in the cytoplasm for envelopment and budding during the late stage of infection (8, 9). Both M1 and NS2 proteins are involved in the nuclear export of vRNPs (10, 11). NS2 protein was renamed "nuclear export protein" (NEP) because it has been confirmed to feature in purified virus particles and to function as a nuclear export protein for vRNPs (11)(12)(13)(14).Segment 8 of influenza A virus encodes two proteins, namely, NS1 and NEP, via differential spli...