Menin prevents liver steatosis through co-activation of peroxisome proliferator-activated receptor alpha

AbstractFatty liver is strongly associated with metabolic syndrome. Here, we show that the impaired hepatic expression of menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, represents a common feature of several fatty liver mouse models. The liver specific ablation of MEN1 gene expression in healthy mice induced hepatic steatosis under high-fat dietary conditions. Moreover, overexpression of menin in livers of steatotic db/db mice reduced liver triglyceride accumulation. At the molecular level, we found that menin acts synergistically with the nuclear receptor PPARα to control gene expression of fatty acid oxidation. Collectively, these data suggest a crucial role for menin as an integrator of the complex transcriptional network controlling hepatic steatosis.Structured summary of protein interactionsMenin physically interacts with PPAR alpha by anti tag coimmunoprecipitation (View Interaction: 1, 2)

Peripheral Leukocytapheresis Attenuates Acute Lung Injury Induced by Lipopolysaccharide In Vivo

The mortality of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains high and efforts for prevention and treatments have shown little improvement over the past decades. The present study investigated the efficacy and mechanism of leukocytapheresis (LCAP) to partially eliminate peripheral neutrophils and attenuate lipopolysaccharide (LPS)-induced lung injury in dogs. A total of 24 healthy male mongrel dogs were enrolled and randomly divided into LPS, LCAP and LCAP-sham groups. All animals were injected with LPS to induce endotoxemia. The serum levels of leucocytes, neutrophil elastase, arterial blood gas, nuclear factor-kappa B (NF-κB) subunit p65 in lung tissues were measured. The histopathology and parenchyma apoptosis of lung tissues were examined. We found that 7, 3, and 7 animals in the LPS, LCAP, and sham-LCAP groups, respectively, developed ALI 36 h after LPS infusion. The levels of NF-κB p65 in lung tissue, neutrophils and elastase in blood, decreased significantly following LCAP. LCAP also alleviated apoptosis, and NF-κB p65 in lung tissues. Collectively, our results show that partial removal of leucocytes from peripheral blood decreases elastase level in serum. This, in turn, attenuates lung injuries and may potentially decrease the incidence of ALI

A Peptide That Binds Specifically to the β-Amyloid of Alzheimer's Disease: Selection and Assessment of Anti-β-Amyloid Neurotoxic Effects

The accumulation of the amyloid-β peptide (Aβ) into amyloid plaques, an essential event in Alzheimer's disease (AD) pathogenesis, has caused researchers to seek compounds that physiologically bind Aβ and modulate its aggregation and neurotoxicity. In order to develop new Aβ-specific peptides for AD, a randomized 12-mer peptide library with Aβ1-10 as the target was used to identify peptides in the present study. After three rounds of selection, specific phages were screened, and their binding affinities to Aβ1-10 were found to be highly specific. Finally, a special peptide was synthesized according to the sequences of the selected phages. In addition, the effects of the special peptide on Aβ aggregation and Aβ-mediated neurotoxicity in vitro and in vivo were assessed. The results show that the special peptide not only inhibited the aggregation of Aβ into plaques, but it also alleviated Aβ-induced PC12 cell viability and apoptosis at appropriate concentrations as assessed by the cell counting kit-8 assay and propidium iodide staining. Moreover, the special peptide exhibited a protective effect against Aβ-induced learning and memory deficits in rats, as determined by the Morris water maze task. In conclusion, we selected a peptide that specifically binds Aβ1-10 and can modulate Aβ aggregation and Aβ-induced neuronal damage. This opens up possibilities for the development of a novel therapeutic approach for the treatment of AD

Pringle manoeuvre versus selective hepatic vascular exclusion in partial hepatectomy for tumours adjacent to the hepatocaval junction: A randomized comparative study

AbstractObjectiveTo compare the efficacy of selective hepatic vascular exclusion versus Pringle manoeuvre in partial hepatectomy for tumours adjacent to the hepatocaval junction.MethodsA randomized comparative trial was carried out. The primary endpoint was intraoperative blood loss. The secondary endpoints were operation time, blood transfusion, postoperative liver function recovery, procedure-related morbidity and in-hospital mortality.Results160 patients were randomized into 2 groups: the Pringle manoeuvre group (n = 80) and the selective hepatic vascular exclusion (SHVE) group (n = 80). Intraoperative blood loss and transfusion requirements were significantly less in the SHVE group. In the SHVE group, laceration of hepatic veins happened in 18 patients. Profuse intraoperative blood loss of over 2 L happened in 2 patients but no patient suffered from air embolism because the hepatic veins were controlled. In the Pringle group, the hepatic veins were lacerated in 20 patients, with profuse blood loss of over 2 L in 7 patients and air embolism in 3 patients. The rates of postoperative bleeding, reoperation, liver failure and mortality were significantly higher and the ICU stay and hospital stay were significantly longer in the Pringle group.ConclusionsSHVE was more efficacious than Pringle manoeuvre for partial hepatectomy in patients with tumours adjacent to the hepatocaval junction

Energy dependence of light (anti)nuclei and (anti)hypertriton production in the Au-Au collision from sNN=5.0\sqrt{s_{\rm{NN}}} =5.0 to 50205020 GeV

The energy dependence of light (anti)nuclei and (anti)hypertriton production are investigated in central Au-Au collisions from AGS up to LHC energies at midrapidity, using the parton and hadron cascade model (PACIAE) together with the dynamically constrained phase-space coalescence model(DCPC). We find that the yields, yield ratios of the antiparticles to their corresponding particles, the coalescence parameters $B_A$ and the strangeness population factor $s_3$ of light (anti)nuclei and (anti)hypertriton strongly depend on the energy. Furthermore, we analyze and discuss the strangeness population factor $s_3$ and the coalescence parameters $B_A$, and find a transition point near by 20 GeV. These results thus suggest the potential usefulness of the $s_3$ and $B_A$ of light nuclei production in relativistic heavy-ion collisions as a direct probe of the transition point associated with the QCD critical phenomena. The results from PACIAE+DCPC model are well consistent with experimental data