CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model.

PURPOSE: CKD-516 is a benzophenone analog in which the B ring is modified by replacement with a carbonyl group. The study assessed CKD-516 as a vascular disrupting agent or anti-cancer drug. METHODS: To assess the effect of S516 on vascularization, we analyzed the effect on human umbilical vein endothelial cells (HUVECs). To determine the inhibition of cell proliferation of S516, we used H460 lung carcinoma cells. The alteration of microtubules was analyzed using immunoblot, RT-PCR and confocal imaging. To evaluate the anti-tumor effects of gemcitabine and/or CKD-516, H460 xenograft mice were treated with CKD-516 (2.5 mg/kg) and/or gemcitabine (40 mg/kg), and tumor growth was compared with vehicle-treated control. For histologic analysis, liver, spleen and tumor tissues from H460 xenograft mice were obtained 12 and 24 h after CKD-516 injection. RESULTS: Cytoskeletal changes of HUVECs treated with 10 nM S516 were assessed by immunoblot and confocal imaging. S516 disrupted tubulin assembly and resulted in microtubule dysfunction, which induced cell cycle arrest (G2/M). S516 markedly enhanced the depolymerization of microtubules, perhaps due to the vascular disrupting properties of S516. Interestingly, S516 decreased the amount of total tubulin protein in HUVECs. Especially, S516 decreased mRNA expression α-tubulin (HUVECs only) and ß-tubulin (HUVECs and H460 cells) at an early time point (4 h). Immunocytochemical analysis showed that S516 changed the cellular microtubule network and inhibited the formation of polymerized microtubules. Extensive central necrosis of tumors was evident by 12 h after treatment with CKD-516 (2.5 mg/kg, i.p.). In H460 xenografts, CKD-516 combined with gemcitabine significantly delayed tumor growth up to 57 % and 36 % as compared to control and gemcitabine alone, respectively. CONCLUSION: CKD-516 is a novel agent with vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy.

Photocatalytic degradation of methylene blue under visible light by cobalt ferrite nanoparticles/graphene quantum dots.

A simple approach was developed to synthesize cobalt ferrite nanoparticles/graphene quantum dots (CF/GQDs). The material was prepared from a homogeneous mixture of iron nitrate, cobalt nitrate, and starch at 140, 180 and 200 °C in a 24 h thermal hydrolysis process. The obtained materials were characterised by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, vibrating-sample magnetometry, and nitrogen adsorption/desorption isotherms. Cobalt ferrite crystals of around 8-10 nm and graphene quantum dots formed directly at 200 °C. Stacking GQDs sheets onto the CF nanoparticles resulted in CF/GQDs nanoparticles. The nanocomposite exhibits satisfactory fluorescent and superparamagnetic properties, which are vital for catalytic applications. The CF/GQDs catalyse significantly the degradation of methylene blue (MB) under visible light. The catalyst can be recycled with an external magnetic field and displays suitable stability. Also, it was reused in three successive experiments with a loss of efficiency of about 5%. The CF/GQDs are considered as an efficient photocatalyst for MB degradation and other dyes.

Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease.

BACKGROUND: Early-onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD. METHODS: To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation-dependent probe amplification kit was used to determine EOPD patients that carried mutations in PRKN and PINK1 genes. RESULTS AND CONCLUSION: Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected in the EOPD cohorts. Mutations of PRKN and PINK1 genes were found in five (4.4%) patients, which were four patients with compound heterozygous variants in the PRKN and one case with a homozygous mutation of the PINK1 gene. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules. The frequency of homozygous mutant genotype p.A340T of the PINK1 in the EOPD cohort was higher than in control (p = 0.0001, OR = 5.704), suggesting this variant might be a risk factor for EOPD. To the best of our knowledge, this is the first study of PRKN and PINK1 genes conducted on Vietnamese EOPD patients. These results might contribute to the genetic screening of EOPD in Vietnam.

Implementation of C-reactive protein point of care testing to improve antibiotic targeting in respiratory illness in Vietnamese primary care (ICAT): a study protocol for a cluster randomised controlled trial.

INTRODUCTION: C-reactive protein (CRP), a biomarker of infection, has been used widely in high-income settings to guide antibiotic treatment in patients presenting with respiratory illnesses in primary care. Recent trials in low- and middle-income countries showed that CRP testing could safely reduce antibiotic use in patients with non-severe acute respiratory infections (ARIs) and fever in primary care. The studies, however, were conducted in a research-oriented context, with research staff closely monitoring healthcare behaviour thus potentially influencing healthcare workers' prescribing practices. For policy-makers to consider wide-scale roll-out, a pragmatic implementation study of the impact of CRP point of care (POC) testing in routine care is needed. METHODS AND ANALYSIS: A pragmatic, cluster-randomised controlled trial, with two study arms, consisting of 24 commune health centres (CHC) in the intervention arm (provision of CRP tests with additional healthcare worker guidance) and 24 facilities acting as controls (routine care). Comparison between the treatment arms will be through logistic regression, with the treatment assignment as a fixed effect, and the CHC as a random effect. With 48 clusters, an average of 10 consultations per facility per week will result in approximately 520 over 1 year, and 24 960 in total (12 480 per arm). We will be able to detect a reduction of 12% to 23% or more in immediate antibiotic prescription as a result of the CRP POC intervention. The primary endpoint is the proportion of patient consultations for ARI resulting in immediate antibiotic prescription. Secondary endpoints include the proportion of all patients receiving an antibiotic prescription regardless of ARI diagnosis, frequency of re-consultation, subsequent antibiotic use when antibiotics are not prescribed, referral and hospitalisation. ETHICS AND DISSEMINATION: The study protocol was approved by the Oxford University Tropical Research Ethics Committee (OxTREC, Reference: 53-18), and the ethical committee of the National Hospital for Tropical Diseases in Vietnam (Reference:07/HDDD-NDTW/2019). Results from this study will be disseminated via meetings with stakeholders, conferences and publications in peer-reviewed journals. Authorship and reporting of this work will follow international guidelines. TRIAL REGISTRATION DETAILS: NCT03855215; Pre-results.

Extraction of uranium from simulated ore by the supercritical carbon dioxide fluid extraction method with nitric acid-TBP complex.

The supercritical fluid extraction (SFE) method using CO(2) as a medium with an extractant of HNO(3)-tri-n-butyl phosphate (TBP) complex was applied to extract uranium from several uranyl phosphate compounds and simulated uranium ores. An extraction method consisting of a static extraction process and a dynamic one was established, and the effects of the experimental conditions, such as pressure, temperature, and extraction time, on the extraction of uranium were ascertained. It was found that uranium could be efficiently extracted from both the uranyl phosphates and simulated ores by the SFE method using CO(2). It was thus demonstrated that the SFE method using CO(2) is useful as a pretreatment method for the analysis of uranium in ores.