Radiosynthesis of a novel antisense imaging probe targeting LncRNA HOTAIR in malignant glioma.

BACKGROUND: Long non-coding RNA (LncRNA) HOTAIR was amplified and overexpressed in many human carcinomas, which could serve as a useful target for cancer early detection and treatment. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to evaluate whether liposome-coated antisense oligonucleotide probe 99mTc-HYNIC-ASON targeting HOTAIR can be used in in vivo imaging of HOTAIR in malignant glioma xenografts. METHODS: The ASON targeting LncRNA HOTAIR as well as mismatched ASON (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC (Instant thin-layer chromatography) and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after liposome-coated 99mTc-HYNIC-ASON/ASONM were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software. RESULTS: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ± 1.5) % and (90 ± 0.6) %, respectively, and both radiochemical purities were more than 89%. Two probes showed good stability within 12 h. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Biodistribution study demonstrated that liposome-coated antisense probes were excreted mainly through the kidney and bladder and has higher uptake in the tumor. Meanwhile, the tumor was clearly shown after injection of liposome coated 99mTc-HYNIC-ASON, and its T/M ratio was higher than that in the non-transfection group and mismatched group. No tumor was seen in mismatched and blocking group. CONCLUSION: The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of LncRNA HOTAIR expression in malignant glioma.

Dental Cleaning, Community Water Fluoridation and Preterm Birth, Massachusetts: 2009-2016.

Objectives Data on the potential effect of dental cleaning and community water fluoridation (CWF) on pregnancy outcomes are scarce. While numerous studies confirm the cost-effectiveness of fluoride in preventing dental caries, the benefit of CWF during pregnancy has not been well established. Methods This cross-sectional study used data from 2009 to 2016 Massachusetts Pregnancy Risk Assessment Monitoring System and restricted to singleton live births (n = 9234, weighted response rate = 64.3%). Our exposures were: (1) dental cleaning alone during pregnancy; (2) CWF alone; and (3) dental cleaning and CWF combined (DC-CWF). Women without dental cleaning during pregnancy and CWF comprised our reference group. The outcome was preterm birth, (birth < 37 weeks gestation). This study used multivariate logistic regression modeling, controlling for maternal sociodemographic characteristics, previous medical risk and behavioral factors, and calculated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results During 2009-2016, the prevalence of preterm birth among women with a singleton live birth was 8.5% in Massachusetts. Overall, 58.7% of women had dental cleaning during pregnancy, and 63.6% lived in CWF. After adjusting for potential confounders, the associations between dental cleaning alone and preterm birth (aRR = 0.74 [95% CI 0.55-0.98]), and DC-CWF and preterm birth (aRR = 0.74 [95% CI 0.57-0.95]) were significant, while the association between CWF alone and preterm birth was not significant (aRR = 0.81 [95% CI 0.63-1.05]), compared to women without dental cleaning and CWF. Conclusions for Practice This study shows that the prevalence of preterm birth was lower among women with DC only and DC-CWF.

Assessment of relationship between aging and contaminant-carryover for different filter layer of surgical mask under urban environmental stressors.

Abundant disposable surgical masks (SMs) remain in the environment and continue to age under urban environmental stressors. This study aimed to investigate the aging characteristics of SMs and the effect of different aged layers of SMs on phenanthrene (PHE), tylosin (TYL), and sulfamethazine (SMT) under two different urban environmental stressors (UV and ozone). The results show that UV exposure causes more severe aging of the SM layers than ozone. The middle layer, made of melt-brown fabric, has displayed the highest degree of aging due to its smaller diameter and mechanical strength. The two-dimensional correlation spectroscopy (2D-COS) analysis reveals the different aging sequences of functional groups and three layers in aged SMs under the two urban environmental stressors. Whether the SMs are aged or not, the adsorptions of three organic pollutants on SMs are positively correlated with the octanol-water partition coefficient. Furthermore, except for the dominant hydrophobic interaction, aged SMs can promote the adsorption of three organic pollutants by accessory interactions (hydrogen bonding and partition), depending on their structures. These findings highlight the environmental effects of new microplastic (MP) sources and coexisting pollutants under the influence of COVID-19, which is helpful in accurately evaluating the biological toxicity of SMs.

Biosafety and efficacy evaluation of a biodegradable magnesium-based drug-eluting stent in porcine coronary artery.

Although the drug-eluting stent (DES) has become the standard for percutaneous coronary intervention (PCI)-based revascularization, concerns remain regarding the use of DES, mainly due to its permanent rigid constraint to vessels. A drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be absorbed entirely after its therapeutic period. Magnesium (Mg)-based BRSs have attracted a great deal of attention due to their suitable mechanical properties, innovative chemical features, and well-proven biocompatibility. However, the primary disadvantage of Mg-based BRSs is the rapid degradation rate, resulting in the early loss of structural support long before the recovery of vascular function. Recently, a new type of patented Mg-Nd-Zn-Zr alloy (JDBM) was developed at Shanghai Jiao Tong University to reduce the degradation rate compared to commercial Mg alloys. In the present investigation, a poly(D,L-lactic acid)-coated and rapamycin eluting (PDLLA/RAPA) JDBM BRS was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The degree of smooth muscle cell adhesion to the PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES FIREHAWK were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analyses were performed 180 days after stent implantation to evaluate the technical feasibility, biocompatibility, and degradation characteristics of JDBM BRS in vivo. The results show the ability of a PDLLA/RAPA coated JDBM to inhibit smooth muscle cell adhesion and moderate the drug release rate of JDBM BRS in vitro. In vivo, low local and systemic risks of JDBM BRS were demonstrated in the porcine model, with preserved mechanical integrity after 6 months of implantation. We also showed that this novel BRS was associated with a similar efficacy profile compared with standard DES and high anti-restenosis performance. These findings may confer long term advantages for using this BRS over a traditional DES.