Effective Treatment of Knee Osteoarthritis Using a Nano-Enabled Drug Acupuncture Technology in Mice.

A nano-enabled drug delivery acupuncture technology (nd-Acu) is developed that is based on traditional acupuncture needles where the stainless-steel surface is designed to deliver various payload molecules. To create the nd-Acu platform, an electrochemistry procedure is used to attach methyl salicylate-modified cyclodextrin in which the sugar rings allow the encapsulation of structurally defined single or multiple payload molecules via an inclusion complexation process. Drug loading and release profile are first studied using fluorescent dyes abiotically and at intact animal level.

Pulmonary Delivery of Specialized Pro-Resolving Mediators-Based Nanotherapeutics Attenuates Pulmonary Fibrosis in Preclinical Animal Models.

Pulmonary fibrosis (PF) is a chronic lung disease characterized by excess extracellular matrix deposition and prolonged inflammation that fails to resolve and is druggable. Using resolvins and their precursors for inflammation resolution, we demonstrate a nano-enabled approach for accomplishing robust antifibrotic effects in bleomycin- or engineered nanomaterial-induced mouse and rat PF models. Targeting the lipid peroxidation-triggered NLRP3 inflammasome and NF-κB pathway in macrophages and the ROS-mediated TGF-β/Smad and S1P signaling in epithelial cells results in these potent protective effects at the ng/mL dosimetry.

A Totipotent "All-In-One" Peptide Sequentially Blocks Immune Checkpoint and Reverses the Immunosuppressive Tumor Microenvironment.

Immune checkpoint blockade combined with reversal of the immunosuppressive tumor microenvironment (TME) can dramatically enhance anti-tumor immunity, which can be achieved by using multiple-agent therapy. However, the optimal dose and order of administration of different agents remain elusive. To address this dilemma, multiple agents are often grafted together to construct "all-in-one" totipotent drugs, but this usually comes at the cost of a lack of synergy between the agents.

Preparation and MRI performance of a composite contrast agent based on palygorskite pores and channels binding effect to prolong the residence time of water molecules on gadolinium ions.

Herein, gadolinium tannate was simply and conveniently coated on the surface of palygorskite by reaction of a coordination polymer formed between tannic acid and Gd. The palygorskite-tannate gadolinium-polyvinyl alcohol integrated composite (PAL@Gd@PVA) is successfully prepared after the introduction of polyvinyl alcohol onto the palygorskite-tannate gadolinium. The structure is characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy analysis.

Tannin-Mn coordination polymer coated carbon quantum dots nanocomposite for fluorescence and magnetic resonance bimodal imaging.

The MR/FI bimodal imaging has attracted widely studied due to combining the advantages of MRI and FI can bridge gaps in sensitivity and depth between these two modalities. Herein, a novel MR/FI bimodal imaging probe is facile fabricated by coating the Mn-phenolic coordination polymer on the surface of the carbon quantum dots. The structure of the as-prepared nanocomposite probe is carefully validated via SEM, TEM, and XPS.

Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis.

Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don't have such an effective anticancer effect even at extremely high concentrations.

Red Fluorescent Emissive Gd-Phenolic Nanoparticles for Fluorescence and Magnetic Resonance Bimodal Imaging.

Due to the combination of the high resolution of fluorescence imaging and the no limitation in penetration depth of magnetic resonance imaging, dual-mode imaging of magnetic resonance and fluorescence (MR/FI) have attracted extensive research in recent years. Herein, a novel MR/FI bimodal imaging probe is facile fabricated by attaching the rhodamine fluorophore covalently to the surface of the Gd-phenolic coordination polymer nanoparticles. The contents of Gd and RB of the as prepared probe are calculated to be 8.

Ultrasensitive Gastric Cancer Circulating Tumor Cellular RNA Detection Based on a Molecular Beacon.

Gastric cancer (GC) is a major global cancer burden, and only HER2-targeted therapies have been approved in first line clinical therapy. CLDN18.2 has been regarded as a potential therapeutic target for gastrointestinal tumors, and global clinical trials have been in process.

Analysis of salivary exosomal proteins in young adults with severe periodontitis.

Objectives: Salivary exosomes harbour numerous constituents associated with oral and systemic diseases. However, no reports addressed components of salivary exosomes in patients with periodontitis. Our study aims to explore salivary exosomal proteins in young adults with severe periodontitis (SP) and to analyse the relationships between different proteins.

A Novel Peptide Probe for Identification of PLS3-Expressed Cancer Cells.

The T-plastin (PLS3) has a significant implication in epithelial-mesenchymal transition (EMT) and breast cancer prognosis. Using one-bead-one-compound library strategy, a novel peptide TP1 (KVKSDRVC) toward PLS3 was screened and exhibited the specificity for identifying PLS3-expressed cancer cells. Moreover, we found Fluorescein isothiocyanate-labeled TP1 (FITC-TP1) could act as a novel probe for EMT-induced cancer cells, preferentially in the leading edge.

Plastin 3 down-regulation augments the sensitivity of MDA-MB-231 cells to paclitaxel via the p38 MAPK signalling pathway.

Plastin 3 (PLS3) overexpression may serve as a marker for predicting chemotherapeutic outcomes in drug-resistant cancer cells, but the mechanism is unclear. Herein, we show that the down-regulation of PLS3 by PLS3 gene silencing augments the sensitivity of MDA-MB-231 triple-negative breast cancer cells to paclitaxel. Interestingly, a low concentration of paclitaxel was able to induce strong apoptosis in the PLS3-silenced cells.

Quantitative proteomic analysis to the first commercialized liposomal paclitaxel nano-platform Lipusu revealed the molecular mechanism of the enhanced anti-tumor effect.

The first nano-platform commercialized as a drug delivery system was a liposomal formulation. The application of liposome technology resolved the issues of paclitaxel (PTX) insolubility and eliminated the use of solvents causing toxic side-effects, which enabled to apply higher drug doses leading to an enhanced drug efficacy. The growth-inhibitory activity of liposome-encapsulated PTX was retained in vitro against a variety of tumor cell.

Quantitative Proteomic Analysis of Cell Responses to Electroporation, a Classical Gene Delivery Approach.

Electroporation, as an established nonviral technology for breaching cell membrane, has been accepted for the delivery of nucleic acids. Despite satisfactory delivery efficiencies have been achieved on multiple cell kinds by simply exhausting all possible electrical parameters, electroporation is still inefficient, or even invalid, for various kinds of cells. This is largely due to the lack of comprehensive understanding of cell responses to electrical stimulation at biological aspect.

Device To Study the Cell Invasion Behavior and Phenotypic Profile at Single Cell Level.

Multiple methods for investigating cell invasion behavior in vitro have proven useful in exploring the mechanisms behind the epithelial-mesenchymal transition (EMT) and EMT-related tumor cell invasion, for example, by revealing that cell heterogeneity existed in EMT. However, several hypotheses and predictions regarding EMT heterogeneity have remained unproven because of the inability to quantitatively profile cell invasion at the single cell level. Here, we present a microfluidic chip that provides the capability of simultaneously investigating single cell invasion behavior, phenotypic diversity, and responsiveness to anti-invasion drugs.

Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1).

Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (<0.

Response of Human Osteoblast to n-HA/PEEK--Quantitative Proteomic Study of Bio-effects of Nano-Hydroxyapatite Composite.

Nano-sized hydroxyapatite (n-HA) is considered as a bio-active material, which is often mixed into bone implant material, polyetheretherketone (PEEK). To reveal the global protein expression modulations of osteoblast in response to direct contact with the PEEK composite containing high level (40%) nano-sized hydroxyapatite (n-HA/PEEK) and explain its comprehensive bio-effects, quantitative proteomic analysis was conducted on human osteoblast-like cells MG-63 cultured on n-HA/PEEK in comparison with pure PEEK. Results from quantitative proteomic analysis showed that the most enriched categories in the up-regulated proteins were related to calcium ion processes and associated functions while the most enriched categories in the down-regulated proteins were related to RNA process.

Quantitative Proteomic Analysis of Cellular Resistance to the Nanoparticle Abraxane.

Abraxane, an FDA-approved albumin-bound nanoparticle (NP) form of paclitaxel (PTX) to treat breast cancer and nonsmall cell lung cancer (NSCLC), has been demonstrated to be more effective than the original Taxol, the single molecule form. We have established a cell line from NSCLC A549 cells to be resistant to Abraxane. To further understand the molecular mechanisms involved in the NP drug resistance, global protein expression profiles of Abraxane sensitive (A549) and resistant cells (A549/Abr), along with the treatment of Abraxane, have been obtained by a quantitative proteomic approach.

Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.

P-glycoprotein (P-gp) can actively pump paclitaxel (PTX) out of cells and induces drug resistance. Abraxane, a nanoparticle (NP) formulation of PTX, has multiple clinical advantages over the single molecule form. However, it is still unclear whether Abraxane overcomes the common small molecule drug resistance problem mediated by P-gp.

In vitro bioactivity and biocompatibility evaluation of bulk nanostructured titanium in osteoblast-like cells by quantitative proteomic analysis.

Nanostructured titanium prepared by the equal-channel angular pressing route (ECAPed Ti) has shown great promise as an implant material over conventional pure titanium. The aim of this report is to investigate its biological properties, surface performance, and comprehensive biological effects at a molecular level when in contact with cells. Protein expression changes of human osteoblast-like MG-63 in response to polished ECAPed Ti had been profiled by employing stable isotope labelling with amino acids in cell culture (SILAC), using cpTi as control after the same polishing process.

Secretome analyses of Aβ(1-42) stimulated hippocampal astrocytes reveal that CXCL10 is involved in astrocyte migration.

Amyloid-beta (Aβ) aggregation plays an important role in the development of Alzheimer's disease (AD). In the AD brain, amyloid plaques are surrounded by reactive astrocytes, and many essential functions of astrocytes have been reported to be mediated by protein secretion. However, the roles of activated astrocytes in AD progression are under intense debate.

MilQuant: a free, generic software tool for isobaric tagging-based quantitation.

Isobaric tagging techniques such as iTRAQ and TMT are widely used in quantitative proteomics and especially useful for samples that demand in vitro labeling. Due to diversity in choices of MS acquisition approaches, identification algorithms, and relative abundance deduction strategies, researchers are faced with a plethora of possibilities when it comes to data analysis. However, the lack of generic and flexible software tool often makes it cumbersome for researchers to perform the analysis entirely as desired.

Quantitative proteomic analysis of human osteoblast-like MG-63 cells in response to bioinert implant material titanium and polyetheretherketone.

Commercially pure titanium (cpTi) and polyetheretherketone (PEEK) are widely used surface-modified implant materials in orthopedics and dental therapeutics. However, there still has not been comprehensive biocompatibility evaluation of them at molecular level. By employing stable isotope labeling with amino acids in cell culture (SILAC), we profiled the dynamic protein expression changes in human osteoblast-like MG-63 cells cultured on cpTi and PEEK, respectively.

Cell responses to two kinds of nanohydroxyapatite with different sizes and crystallinities.

Introduction: Hydroxyapatite (HA) is the principal inorganic constituent of human bone. Due to its good biocompatibility and osteoconductivity, all kinds of HA particles were prepared by different methods. Numerous reports demonstrated that the properties of HA affected its biological effects.