N-Terminal Myristoylated VP5 is Required for Penetrating Cell Membrane and Promoting Infectivity in Aquareoviruses

正Dear Editor,Myristoylation is a naturally occurring post-translational modification for targeting cytoplasmic proteins to intracellular membranes.Unlike enveloped animal viruses,which enter host cells by membrane fusion,nonenveloped animal viruses must disrupt the cell membrane to initiate infection.Some animal viruses and several nonenveloped viruses such     

ADFP promotes cell proliferation in lung adenocarcinoma via Akt phosphorylation

Previously, we identified differentially expressed proteins, including ADFP, between lung adenocarcinoma (LAC) tissue and paired normal bronchioloalveolar epithelium. In this study, we investigated the role of ADFP in LAC. ADFP levels in the serum of patients with lung cancer and benign diseases were measured by enzyme-linked immunosorbent assays (ELISA). shRNA was used to knock-down or overexpress ADFP in A549 and NCI-H1299 cells. The biological function of ADFP and its underlying mechanisms was evaluated in vivo and in vitro. ADFP was highly expressed in the serum of lung cancer patients, especially those with LAC. ADFP promoted cell proliferation and up-regulated the p-Akt/Akt ratio in A549 and NCI-H1299 cells in vitro. Furthermore, in nude mice, ADFP promoted tumour formation with high levels of p-Akt/Akt, Ki67 and proliferating cell nuclear antigen (PCNA). Similar to the effect of ADFP knock-down, MK-2206 (a phosphorylation inhibitor of Akt) reduced A549 and NCI-H1299 cell proliferation. In ADFP-overexpressing A549 and NCI-H1299 cells, proliferation was suppressed by MK-2206 and returned to the control level. ADFP did not regulate invasion, migration or adhesion in LAC cells. Together, these results suggest that ADFP promotes LAC cell proliferation in vitro and in vivo by increasing Akt phosphorylation level.     

Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway

Background: Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25–30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.Methods: After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.Results: Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC₅₀ were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G₂/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.Conclusions: Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.     

Freezing of phosphocholine headgroup in fully hydrated sphingomyelin bilayers and its effect on the dynamics of nonfreezable water at subzero temperatures.

Differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR) spectroscopy are applied to characterize the nonfreezable water molecules in fully hydrated D2O/sphingomyelin at temperatures below 0 degrees C. Upon cooling, DSC thermogram displays two thermal transitions peaked at -11 and -34 degrees C. The high-temperature exothermic transition corresponds to the freezing of the bulk D2O, and the low-temperature transition, which has not previously been reported, can be ascribed to the freezing of the phosphocholine headgroup in the lipid bilayer. The dynamics of nonfreezable water are also studied by 2H NMR T1 (spin-lattice relaxation time) and T2e (spin-spin relaxation time obtained by two pulse echo) measurements at 30.7 MHz and at temperatures down to -110 degrees C. The temperature dependence of the T1 relaxation time is characterized by a distinct minimum value of 2.1 +/- 0.1 ms at -30 degrees C. T2e is discontinuous at temperature around -70 degrees C, indicating another freezing-like event for the bound water at this temperature. Analysis of the relaxation data suggest that nonfreezable water undergoes both fast and slow motions at characteristic NMR time scales. The slow motions are affected when the lipid headgroup freezes.     

A bursal pentapeptide (BPP-I), a novel bursal-derived peptide, exhibits antiproliferation of tumor cell and immunomodulator activity

The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. Here, we isolated a novel bursal pentapeptide I (BPP-I), LGPGP, from BF. BPP-I could play inhibition effect on MCF-7 but not on CEF or Vero cell proliferation in vitro, and enhance antitumor factor p53 protein expression. Also, BPP-I stimulated antibody production in a dose-dependent manner in hybridoma cell. Furthermore, BPP-I could induce various immune responses in mice immunization experiments, including increase antibody production and cytokines IL-4 and IFN-γ level, and induce T-cell immunophenotyping. These results suggest that BPP-I is a potential immunomodulator of antitumor and immunity. The study could provide some novel insights on the probable candidate reagent for the antitumor and immune improvement.     

Combination of fucoxanthin and conjugated linoleic acid attenuates body weight gain and improves lipid metabolism in high-fat diet-induced obese rats

The present study investigated the effects of combined fucoxanthin (Fc) and conjugated linoleic acid (CLA) on high-fat diet-induced obese rats. Thirty five rats were divided into four groups, fed a high-fat diet (Control, 15% fat, wt/wt), supplemented with low Fc (FCL, 0.083 mg/kg/bw), high Fc (FCH, 0.167 mg/kg/bw) and FCL (0.083 mg/kg/bw) plus CLA (0.15 g/kg/bw) (FCL+CLA) for 52 d. Body weight and white adipose tissue (WAT) weight were significantly suppressed in FCL+CLA group than those in control group. WAT weight was also markedly attenuated in FCL and FCH groups. Accumulation of hepatic lipid droplets and the perirenal adipocyte size of FCL, FCH and FCL+CLA groups were diminished compared to control group. Serum total cholesterol level in FCH group, triacylglycerol and leptin levels in FCL, FCH and FCL+CLA groups, and glucose concentration in FCH and FCL+CLA groups were significantly decreased than those in control group. The mRNA expression of adiponectin, adipose triacylglycerol lipase, carnitine palmitoyltransferase 1A was remarkably up-regulated in FCL, FCH and FCL+CLA groups. These results suggest that Fc and FCL+CLA could reduce serum levels of triacylglycerol, glucose and leptin, and FCL+CLA could exert anti-obesity effects by regulating mRNA expression of enzymes related to lipid metabolism in WAT of diet-induced obesity rats.     

Hydrogen sulfide decreases the levels of ROS by inhibiting mitochondrial complex IV and increasing SOD activities in cardiomyocytes under ischemia/reperfusion

Inhibition of oxidative stress has been reported to be involved in the cardioprotective effects of hydrogen sulfide (H(2)S) during ischemia/reperfusion (I/R). However, the mechanism whereby H(2)S regulates the level of cardiac reactive oxygen species (ROS) during I/R remains unclear. Therefore, we investigated the effects of H(2)S on pathways that generate and scavenge ROS. Our results show that pretreating rat neonatal cardiomyocytes with NaHS, a H(2)S donor, reduced the levels of ROS during the hypoxia/reoxygenation (H/R) condition. We found that H(2)S inhibited mitochondrial complex IV activity and increased the activities of superoxide dismutases (SODs), including Mn-SOD and CuZn-SOD. Further studies indicated that H(2)S up-regulated the expression of Mn-SOD but not CuZn-SOD. Using a cell-free system, we showed that H(2)S activates CuZn-SOD. An isothermal titration calorimetry (ITC) analysis indicated that H(2)S directly interacts with CuZn-SOD. Taken together, H(2)S inhibits mitochondrial complex IV and activates SOD to decrease the levels of ROS in cardiomyocytes during I/R.     

Design, synthesis and biological evaluation of novel amino acid ureido derivatives as aminopeptidase N/CD13 inhibitors

A series of amino acid ureido derivatives as aminopeptidase N (APN/CD13) inhibitors were synthesized and evaluated for their APN inhibitory activities and anti-cancer effects. The results showed that most of these amino acid ureido derivatives exhibited good inhibition against APN, several of which were better than Bestatin. The most active compound 12j (IC(50) = 1.1 μM, compared with Bestatin IC(50) = 8.1 μM) not only possessed much better APN inhibitory activity and anti-proliferation effect on cancer cells, but also exhibited significant block effect of human cancer cell invasion compared with the positive control, Bestatin. These amino acid ureido derivatives could be possibly developed as new APN inhibitors for cancer chemotherapy in the future.     

High Polarity Poly(vinylidene difluoride) Thin Coating for Dendrite‐Free and High‐Performance Lithium Metal Anodes

The high‐polarity β‐phase poly(vinylidene difluoride) (β‐PVDF), which has all trans conformation with F and H atoms located on the opposite sides of the polymer backbone, is demonstrated to be a promising artificial solid‐electrolyte interphase coating on both Cu and Li metal anodes for dendrite‐free Li deposition/stripping and enhanced cycling performance. A thin (≈4 µm) β‐PVDF coating on Cu enables uniform Li deposition/stripping at high current densities up to 5 mA cm^?2, Li‐plating capacity loadings of up to 4 mAh cm^?2, and excellent cycling stability over hundreds of cycles under practical conditions (1 mA cm^?2 with 2 mAh cm^?2). Full cells containing an LiFePO₄ cathode and an anode of either β‐PVDF coated Cu or Li also exhibit excellent cycling stability. The profound effects of the high‐polarity PVDF coating on dendrite suppression are attributed to the electronegative F‐rich interface that favors layer‐by‐layer Li deposition. This study offers a new strategy for the development of dendrite‐free metal anode technology.