Predicting Successes and Failures of Clinical Trials With Outer Product-Based Convolutional Neural Network.

Despite several improvements in the drug development pipeline over the past decade, drug failures due to unexpected adverse effects have rapidly increased at all stages of clinical trials. To improve the success rate of clinical trials, it is necessary to identify potential loser drug candidates that may fail at clinical trials. Therefore, we need to develop reliable models for predicting the outcomes of clinical trials of drug candidates, which have the potential to guide the drug discovery process.

Prediction of drug-target binding affinity using similarity-based convolutional neural network.

Identifying novel drug-target interactions (DTIs) plays an important role in drug discovery. Most of the computational methods developed for predicting DTIs use binary classification, whose goal is to determine whether or not a drug-target (DT) pair interacts. However, it is more meaningful but also more challenging to predict the binding affinity that describes the strength of the interaction between a DT pair.

Blocking C-Raf alleviated high-dose small-volume radiation-induced epithelial mesenchymal transition in mice lung.

The goal of this study was to develop a potential druggable target for lung injury after SABR through the small animal model. Utilising the model, a radiation dose of 70 Gy or 90 Gy was focally (small volume) delivered to the left lung of mice. The highly expressed phosphorylation form of C-Raf was discovered through a protein array experiment, with the protein being extracted from the area of radiated mouse lung tissue, and was confirmed by IHC and western blot.

Zwitterionic pH-responsive hyaluronic acid polymer micelles for delivery of doxorubicin.

As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.

Risk factors to identify patients who may not benefit from whole brain irradiation for brain metastases - a single institution analysis.

Background: Radiotherapy plays a major role in the management of brain metastases. This study aimed to identify the subset of patients with multiple brain metastases who may not benefit from whole brain irradiation (WBI) due to a short survival time regardless of treatment.

Methods: We analyzed a total of 339 patient records with brain metastases treated with whole brain radiotherapy from January 2009 to January 2016.

Synthesis, Characterization and Cytotoxicity of Alkylated Quercetin Derivatives.

Quercetin, a ubiquitous flavonol, represents a promising leading drug for development of new chemotherapeutic agents. However, its limited cytotoxicity to cancer cells hampers its clinical use. In order to obtain novel quercetin derivatives with superior cytotoxicity, seven alkylated quercetin derivatives were synthesized.

The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes.

Background: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes.

Methods: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats.

Time, Dose, and Volume Responses in a Mouse Pulmonary Injury Model Following Ablative Irradiation.

Purpose: We aimed to determine the time, dose, and volume responses in a mouse pulmonary injury model following ablative dose focal irradiation (ADFIR) in order to better understand normal lung injury.

Methods And Materials: ADFIR was administered to the left lung of mice using a small animal micro-irradiator. Histopathological evaluation and micro-computed tomography (micro-CT) analyses were performed at 1, 2, 6, and 12 weeks after irradiation.

Observation of orbital angular momentum transfer from bessel-shaped acoustic vortices to diphasic liquid-microparticle mixtures.

We observe distinct regimes of orbital angular momentum (OAM) transfer from two-dimensional Bessel-shaped acoustic vortices to matter. In a homogeneous diphasic mixture of microparticles and water, slow swirling about the vortex axis is seen. This effect is driven by the absorption of OAM across the mixture, the motion following the OAM density distribution.

A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.

Experimental Design/results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF.

[Pollution characteristics of platinum group elements in road rust in Xiamen].

With the potential risks for the environment and human health, the concentration and distribution characteristics of platinum group element(PGEs) in road dust in Xiamen city were investigated. Road dust samples were collected from the traffic trunk road, tunnel, tourism area, and industrial area of Xiamen on October 2012. The samples were digested with aqua regia in a microwave assisted digestion system under high pressure condition, separated and purified with cation exchange resin( Dowex AG50W-X8), and the resulting solutions were analyzed by inductively coupled plasma mass spectrometry (ICP-MS).

An experimental model-based exploration of cytokines in ablative radiation-induced lung injury in vivo and in vitro.

Introduction: Stereotactic ablative radiotherapy is a newly emerging radiotherapy treatment method that, compared with conventionally fractionated radiation therapy (CFRT), allows an ablative dose of radiation to be delivered to a confined area around a tumor. The aim of the present study was to investigate the changes of various cytokines that may be involved in ablative radiation-induced lung injury in vitro and in vivo.

Methods: In the in vivo study, ablative-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal irradiator.

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator.

Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries.

Given the tremendous potential of stereotactic body radiotherapy (SBRT), investigations of the underlying radiobiology associated with SBRT-induced normal tissue injury are of paramount importance. This study was designed to develop an animal model that simulates centrally and peripherally located clinical SBRT-induced lung injuries. A 90-Gy irradiation dose was focally delivered to the central and peripheral areas of the left mouse lung with an image-guided small-animal irradiation system.

Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation.

A porcine skin model was developed to characterize the dose-dependent response to high-dose radiation. The dorsal skin of a mini pig was divided into four paraspinal sections, with 11 small irradiation fields (2 cm × 2 cm) in each section, and a single fraction of 15, 30, 50 or 75 Gy was delivered to each section using a 6 MeV electron beam. A spectrophotometer measured gross skin changes, and a biopsy for each radiation dose was performed in the 1st, 2nd, 4th, 6th and 9th weeks for histology, immunostaining with anti-CD31, and western blotting with IL-6 and TGF-β1 to determine the degree of skin damage.

Therapeutic effects of water soluble danshen extracts on atherosclerosis.

Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE.

Inhibition of Akt/FOXO3a signaling by constitutively active FOXO3a suppresses growth of follicular thyroid cancer cell lines.

Akt-dependent FOXO3a cytoplasmic translocation is an important tumorigenic mechanism for escaping from apoptosis in cancer cells. In the present study, we examined whether non-phosphorylatable FOXO3a can inhibit cell growth of various follicular thyroid carcinoma (FTC) cell lines. Adenovirus carrying the FOXO3a-triple mutant (TM) sequence including point mutations at three Akt phosphorylation sites (Ad-FOXO3a-TM) was generated and transduced to the cells to mimic inhibition of Akt/FOXO3a signal.

Cytotoxicity of natural extract from Tegillarca granosa on ovarian cancer cells is mediated by multiple molecules.

Purpose: To determine the cellular and molecular mechanism of cytotoxicity induced by Haishengsu (HSS), nature extract from Tegillarca granosa, toward human ovarian cancer cell lines SKOV-3 and OVCAR-3.

Methods: The cytotoxic effects of HSS on two ovarian cancer cell lines were tested by XTT assay. Cell apoptosis and cell cycle arrest induced by HSS were demonstrated by DNA ladder assay and flow cytometric analysis, respectively.

Chitosan-alginate microcapsules for oral delivery of egg yolk immunoglobulin (IgY): effects of chitosan concentration.

In our previous study, chitosan-alginate microcapsules were developed to protect egg yolk immunoglobulin (IgY) from gastric inactivation. The present study was undertaken to determine the effect of chitosan concentration (0-0.8%; w/v) on various properties of the microcapsules in order to produce the optimum chitosan-alginate microcapsules for use in the oral delivery of IgY.

Chitosan-alginate microcapsules for oral delivery of egg yolk immunoglobulin (IgY): in vivo evaluation in a pig model of enteric colibacillosis.

In our previous study, the applicability of chitosan-alginate microcapsules for oral delivery of egg yolk immunoglobulin (IgY) was established in a simulated gastrointestinal tract environment. The objective of the present study was to evaluate the protective efficacy of microencapsulated IgY against K88+ ETEC (enterotoxigenic Escherichia coli)-induced diarrhea in 40-day-old pigs. Groups of pigs orally challenged with 10(11) cfu/mL of K88+ ETEC were fed with non-encapsulated IgY, microencapsulated IgY and aureomycin-treated feed respectively.

Efficacy of specific egg yolk immunoglobulin (IgY) to bovine mastitis caused by Staphylococcus aureus.

The objective of this study was to estimate the efficacy of specific egg yolk immunoglobulin (IgY) to bovine mastitis caused by Staphylococcus aureus. Eighteen lactating cows with clinical mastitis and 18 lactating cows with experimental mastitis (1 quarter per cow) were randomly assigned to three treatments: IgY (20mg/ml) infusion, penicillin (100mg/ml) infusion and no infusion. Treatments for clinical mastitis and experimental mastitis were performed by a 6-day course of intramammary infusion with a dosage of 10ml at an interval of 12h.