Characterizing α‑Helical Peptide Aggregation on Supported Lipid Membranes Using Microcantilevers

We report the use of lipid membrane-coated microcantilevers to probe the interactions between phospholipid membranes and membrane-active peptides. This sensing method integrates two well-developed techniques: solid-supported lipid bilayers (SLBs) and microcantilever sensors. SLBs are prepared on the silicon dioxide surface of the microcantilevers using a vesicle fusion method. As molecules adsorb onto the surface of the microcantilever, the microcantilever bends due to the induced compressive or tensile stresses, which result from the surface free energy change. Real-time surface stress changes in the SLB due to interactions with small molecules can be detected by monitoring the deflection of the microcantilever. We investigate the mechanism for the interaction between SLBs and PEP1, a synthetic amphipathic peptide resembling a segment of the nonstructural protein (NS5A) of the hepatitis C virus. Initially, the PEP1 peptides adsorb onto the lipid membranes, and then at a critical concentration, the peptides begin to aggregate and form pores; finally, the peptides destabilize and induce solubilization of the supported membranes. The membrane-coated microcantilever sensor is capable of characterizing the kinetics and dynamics of this process with great sensitivity

Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors

Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with <i>Q</i>² = 0. 64, <i>R</i>²_ncv = 0.93, <i>R</i>²_pred = 0.80 and <i>Q</i>² = 0. 65, <i>R</i>²_ncv = 0.98, <i>R</i>²_pred = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors

Radioactive Tracer Tests of Two Improved TRPO Processes for High-Level Liquid Waste Using Annular Centrifugal Contactors

<div><p>High-level liquid waste (HLLW) produced from the reprocessing of the spent nuclear fuel still contains moderate amounts of uranium, transuranium (TRU) actinides, and fission products, and thus constitutes a permanent hazard to the environment. The partitioning and transmutation (P&T) strategy has increasingly attracted interest for the safe treatment and disposal of HLLW, in which the partitioning of HLLW is one of the critical technical issues. Two improved trialkylphosphine oxide (TRPO) processes for the removal of actinides have been developed to treat Chinese HLLW, based on the original TRPO process. In one improved process <i>N,N</i>-diethylhydroxylamine as a reducing agent was used for reducing Np(V) and Np(VI) to Np(IV) in order to improve the extraction efficiency of Np. In the other improved process, ammonium vanadate as an oxidizing agent was used for oxidizing Np(V) and Np(IV) to Np(VI) in order to improve the extraction efficiency of Np. Radioactive tracer tests of two improved TRPO processes were carried out using 30-stage 10-mm-diam annular centrifugal contactors and simulated HLLW containing U, Np, Pu, and Am. The test results showed that the decontamination factor of total α activity was >1 × 10⁵. During the test, 30-stage 10-mm-diam annular centrifugal contactors worked in a stable manner continuously, with no stage failing or any interruption of the operation.</p></div

Comparison of molecular properties between herbal compounds and DrugBank drugs.

Comparison of molecular properties between herbal compounds and DrugBank drugs.</p

A Methodology for Cancer Therapeutics by Systems Pharmacology-Based Analysis: A Case Study on Breast Cancer-Related Traditional Chinese Medicines

<div><p>Breast cancer is the most common carcinoma in women. Comprehensive therapy on breast cancer including surgical operation, chemotherapy, radiotherapy, endocrinotherapy, etc. could help, but still has serious side effect and resistance against anticancer drugs. Complementary and alternative medicine (CAM) may avoid these problems, in which traditional Chinese medicine (TCM) has been highlighted. In this section, to analyze the mechanism through which TCM act on breast cancer, we have built a virtual model consisting of the construction of database, oral bioavailability prediction, drug-likeness evaluation, target prediction, network construction. The 20 commonly employed herbs for the treatment of breast cancer were used as a database to carry out research. As a result, 150 ingredient compounds were screened out as active molecules for the herbs, with 33 target proteins predicted. Our analysis indicates that these herbs 1) takes a ‘Jun-Chen-Zuo-Shi” as rule of prescription, 2) which function mainly through perturbing three pathways involving the epidermal growth factor receptor, estrogen receptor, and inflammatory pathways, to 3) display the breast cancer-related anti-estrogen, anti-inflammatory, regulation of cell metabolism and proliferation activities. To sum it up, by providing a novel <i>in silico</i> strategy for investigation of the botanical drugs, this work may be of some help for understanding the action mechanisms of herbal medicines and for discovery of new drugs from plants.</p></div

Thioether-Bonded Fluorescent Probes for Deciphering Thiol-Mediated Exchange Reactions on the Cell Surface

Study on the processes of the thiol-mediated disulfide exchange reactions on the cell surface is not only important to our understanding of extracellular natural bioreduction processes but to the development of novel strategies for the intracellular delivery of synthetic bioactive molecules. However, disulfide-bonded probes have their intrinsic inferiority in exploring the detailed exchange pathway because of the bidirectional reactivity of disulfide bonds toward reactive thiols. In this work, we developed thioether-bonded fluorescent probes that enable us to explore thiol-mediated thioether (and disulfide) exchange reactions on the cell surface through fluorescence recovery and/or cell imaging. We demonstrated that our thioether-bonded probes can be efficiently cleaved through thiol-thioether exchanges with exofacial protein thiols and/or glutathione (GSH) efflux. The exchanges mainly take place on the cell surface, and GSH efflux-mediated exchange reactions can take place without the requirement of pre-exchanges of the probes with cell surface-associated protein thiols. On the basis of our founder methodology, for the first time we demonstrated the interplay of exofacial protein thiols and GSH efflux on the cleavage of external thioether-bonded compounds. Moreover, given that an understanding of the process of GSH efflux and the mechanism on which it relies is crucial to our understanding of the cellular redox homeostasis and the mechanism of multidrug resistance, we expect that our thioether-bonded probes and strategies would greatly benefit the fundamental study of GSH efflux in living cells

MOESM1 of LncRNA LUADT1 sponges miR-15a-3p to upregulate Twist1 in small cell lung cancer

Additional file 1: Figure S1. LUADT1 promoted H69 cell invasion and migration through Twist1 and miR-15a-3p.Transwell assays were also carried out to explore the effects of transfections on the invasion (A) and migration (B) of H69 cells. Data were expressed as the mean values of 3 replicates, *p < 0.05

The information of breast cancer targets.

The information of breast cancer targets.</p

150 bioactive compounds of the 20 herbs with their predicted OB and DL values.

<p>150 bioactive compounds of the 20 herbs with their predicted OB and DL values.</p