Aromatic-interaction-mediated inhibition of ß-amyloid assembly structures and cytotoxicity.

Abnormal aggregation of ß-amyloid (Aß) peptide plays an important role in the onset and progress of Alzheimer's disease (AD); hence, targeting Aß aggregation is considered as an effective therapeutic strategy. Here, we studied the aromatic-interaction-mediated inhibitory effect of oligomeric polypeptides (K8Y8, K4Y8, K8W8) on Aß42 fibrillization process. The polypeptides containing lysine as well as representative aromatic amino acids of tryptophan or tyrosine were found to greatly suppress the aggregation as evaluated by thioflavin T assay. Circular dichroism spectra showed that the ß-sheet formation of Aß42 peptides decreased with the polypeptide additives. Molecular docking studies revealed that the oligomeric polypeptides could preferentially bind to Aß42 through π-π stacking between aromatic amino acids and Phe19, together with hydrogen bonding. The cell viability assay confirmed that the toxicity of Aß42 to SH-SY5Y cells was markedly reduced in the presence of polypeptides. This study could be beneficial for developing peptide-based inhibitory agents for amyloidoses. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Dual-affinity peptide mediated inter-protein recognition.

We present for the first time an enhanced interaction affinity between an abundant soluble protein (human serum albumin) and a membrane protein (chemokine receptor 4) mediated by a dual-affinity peptide E5.

Inhibition of ß-amyloid peptide self-assembly and cytotoxicity by poly(LVFF-co-ß-amino ester).

The ß-amyloid (Aß) peptide plays an important role in the onset and progress of Alzheimer's disease (AD). Therefore, studies on inhibiting fibril formation and thus neurotoxicity of Aß could be beneficial for the prevention and treatment of AD. We report a convenient synthetic approach for one-pot preparation of poly-(ß-amino ester) copolymerized with the GGLVFF peptide, which is based on the frequently used inhibitor LVFF. The copolymer was found to efficiently inhibit the aggregation and fibrillation of Aß42 by using fluorescence assay and atomic force microscopy. Reduced ß-sheet formation of Aß42 peptide after addition of copolymer was observed by circular dichroism. Furthermore, the cell viability assay confirmed that the toxicity of Aß42 for SH-SY5Y cells was markedly reduced in the presence of copolymer. This could be beneficial for AD prevention and treatment and also for the molecular design of inhibitory agents for other amyloidoses.

Preliminary Study of Pulsed Ultraviolet Technology for Low-Temperature Disinfection.

Introduction: To explore the feasibility of pulsed ultraviolet (UV) light technology for low-temperature disinfection, a series of experiments were conducted. Methods: Pulsed UV technology's effectiveness in disinfecting Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli on different carriers were studied under varying temperatures. Results: Under different temperatures and constant radiation illumination (i.e., distance), the disinfection effect was correlated with irradiation time; among the three carriers, the disinfection effect of cloth sheets was the best, followed by stainless steel sheets, and corrugated paper sheet. The disinfection effect on Gram-negative bacteria Escherichia coli was better than that on Gram-positive bacteria Staphylococcus aureus overall. Discussion: Temperature has a limited effect on pulsed UV disinfection. Irradiation times and carrier types are influencing factors.

Monitoring the Effective Sterilization of Low-Temperature Hydrogen Peroxide Gas Plasma Sterilizers in 58 Hospitals - 22 PLADs, China, June 2015-December 2019.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Hydrogen peroxide sterilizeation is widely used for luminal devices. However, the low penetrability of the sterilant is of major concern. WHAT IS ADDED BY THIS REPORT?: This report investigated the effective sterilization of low-temperature hydrogen peroxide gas plasma sterilizers and compared the applicability of different biological monitoring methods based on medical luminal devices. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: It is recommended to use a biological process challenge device for monitoring the sterilization of luminal devices with low-temperature hydrogen peroxide gas plasma sterilizers.

Prevention and control of COVID-19 in public transportation: Experience from China.

Due to continuous spread of coronavirus disease 2019 (COVID-19) worldwide, long-term effective prevention and control measures should be adopted for public transport facilities, as they are increasing in popularity and serve as the principal modes for travel of many people. The human infection risk could be extremely high due to length of exposure time window, transmission routes and structural characteristics during travel or work. This can result in the rapid spread of the infection. Based on the transmission characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the nature of public transport sites, we identified comprehensive countermeasures toward the prevention and control of COVID-19, including the strengthening of personnel management, personal protection, environmental cleaning and disinfection, and health education. Multi-pronged strategies can enhance safety of public transportation. The prevention and control of the disease during the use of public transportation will be particularly important when all countries in the world resume production. The aim of this study is to introduce experience of the prevention and control measures for public transportation in China to promote the global response to COVID-19.

Correction: Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

[This corrects the article DOI: 10.1039/C8RA08526A.].

Principles of Inter-Amino-Acid Recognition Revealed by Binding Energies between Homogeneous Oligopeptides.

We have determined the interaction strengths of the common naturally occurring amino acids using a complete binding affinity matrix of 20 × 20 pairs of homo-octapeptides consisting of the 20 common amino acids between stationary and mobile states. We used a bead-based fluorescence assay for these measurements. The results provide a basis for analyzing specificity, polymorphisms, and selectivity of inter-amino-acid interactions. Comparative analyses of the binding energies, i.e., the free energies of association (ΔG A), reveal contributions assignable to both main-chain-related and side-chain-related interactions originating from the chemical structures of these 20 common amino acids. Side-chain-side-chain and side-chain-main-chain interactions are found to be pronounced in an identified set of amino acid pairs that determine the basis of inter-amino-acid recognition.

Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

The metastasis of breast cancer is one of the main factors resulting in the high fatality of patients. Although many antagonists have been developed to inhibit the metastasis of breast cancer, their practical application has been limited because of the poor solubility of many chemotherapeutic drugs in the physiological environment. Herein, a complex of E5 peptide antagonist and acetylated PAMAM G5 (PAC80) has been constructed to enhance the solubility of the peptide antagonist. The E5 peptide antagonist has been designed and it was confirmed that it could specifically bind to CXCR4, which is a chemokine receptor involved in the metastasis of several types of cancers, in our previous work. The results demonstrated that PAC80 could significantly increase the solubility of the E5 peptide in the physiological environment, as well as the affinity of the E5 peptide to CXCR4-positive cell lines, and the inhibitory effect of the E5 peptide for cell migration in vitro. Meanwhile, the passive lung metastasis model of breast cancer was established and the anti-tumor metastasis of the PAC80-E5 complex was evaluated in vivo. The results show that the PAC80-E5 complex demonstrated excellent inhibition for the tumor metastasis at an E5 dosage of 10 and 20 mg kg-1. These effects indicate a feasible strategy to apply the PAC80-peptide complex in cancer therapies to improve the solubility and bioavailability.

Correction: Improving the inhibitory effect of CXCR4 peptide antagonist in tumor metastasis with an acetylated PAMAM dendrimer.

[This corrects the article DOI: 10.1039/C8RA08526A.].

Anti-tumor activity of nanomicelles encapsulating CXCR4 peptide antagonist E5.

Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors.

Improving chemotherapeutic efficiency in acute myeloid leukemia treatments by chemically synthesized peptide interfering with CXCR4/CXCL12 axis.

Bone marrow stroma can protect acute myeloid leukemia (AML) cells against chemotherapeutic agents and provide anti-apoptosis and chemoresistance signals through secreting chemokine CXCL12 to activate its receptor CXCR4 on AML cells, resulting in minimal residual leukemia and relapse. Therefore disrupting the CXCR4/CXCL12 axis with antagonists is of great significance for improving chemosensitivity and decreasing relapse rate. In a previous study, we reported a novel synthetic peptide E5 with its remarkable effect on inhibiting CXCR4/CXCL12-mediated adhesion and migration of AML cells. Here we presented E5's capacity of enhancing the therapeutic efficiency of various chemotherapeutics on AML in vitro and in vivo. Results showed that E5 can diminish bone marrow stromal cell-provided protection to leukemia cells, significantly increasing the apoptosis induced by various chemotherapeutics in multiple AML cell lines. In an AML mouse xenograft model, E5 induced 1.84-fold increase of circulating AML cells out of protective stroma niche. Combined with vincristine or cyclophosphamide, E5 inhibited infiltration of AML cells into bone marrow, liver and spleen, as well as prolonged the lifespan of AML mice compared with mice treated with chemotherapy alone. In addition, E5 presented no toxicity in vivo according to the histological analysis and routine clinical parameters of serum analysis.

Molecular tethering effect of C-terminus of amyloid peptide aß42.

Amyloid peptides are considered to be the main contributor for the membrane disruption related to the pathogenesis of degenerative diseases. The variation of amino acids at the carboxylic terminus of amyloid peptide has revealed significant effects on the modulation of abnormal assemblies of amyloid peptides. In this work, molecular binding agents were tethered to the C-terminus of ß-amyloid peptide 1-42 (Aß42). The molecular interaction between Aß42 and molecule tethers was identified at single molecule level by using scanning tunneling microscopy (STM). The mechanistic insight into the feature variation of the self-assembly of Aß42 peptide caused by molecular tethering at C-terminus was clearly revealed, which could appreciably affect the nucleation of amyloid peptide, thus reducing the membrane disruptions.