Phytoglycogen to Enhance the Solubility and in-vitro Permeation of Resveratrol.

This study investigated the capability of phytoglycogen (PG) to improve the water-soluble amount and bioavailability of resveratrol (RES). RES and PG were incorporated through co-solvent mixing and spray-drying to form PG-RES solid dispersions. The soluble amount of RES of PG-RES solid dispersions reached 289.6 µg/mL at PG:RES ratio of 50:1, compared with 45.6 µg/mL for RES alone. X-ray powder diffraction and Fourier-transform infrared spectroscopy tests suggested a significant reduction of RES crystallinity in PG-RES solid dispersions and the formation of hydrogen bonds between RES and PG. Caco-2 monolayer permeation tests showed that, at low RES loading concentrations (15 and 30 µg/mL), PG-RES solid dispersions achieved greater permeation of RES (0.60 and 1.32 µg/well, respectively) than RES alone (0.32 and 0.90 µg/well, respectively). At an RES loading of 150 µg/mL, PG-RES solid dispersion realized RES permeation of 5.89 µg/well, suggesting the potential of PG in enhancing the bioavailability of RES.

Bioactive superparamagnetic iron oxide-gold nanoparticles regulated by a dynamic magnetic field induce neuronal Ca2+ influx and differentiation.

Treating neurodegenerative diseases, e.g., Alzheimer's Disease, remains a significant challenge due to the limited neuroregeneration rate in the brain. The objective of this study is to evaluate the hypothesis that external magnetic field (MF) stimulation of nerve growth factor functionalized superparamagnetic iron oxide-gold (NGF-SPIO-Au) nanoparticles (NPs) can induce Ca2+ influx, membrane depolarization, and enhance neuron differentiation with dynamic MF (DMF) outperforming static MF (SMF) regulation. We showed the that total intracellular Ca2+ influx of PC-12 cells was improved by 300% and 535% by the stimulation of DMF (1 Hz, 0.5 T, 30min) with NGF-SPIO-Au NPs compared to DMF alone and SMF with NGF-SPIO-Au NPs, respectively, which was attributed to successive membrane depolarization. Cellular uptake performed with the application of sodium azide proved that DMF enhanced cellular uptake of NGF-SPIO-Au NPs via endocytosis. In addition, DMF upregulated both the neural differentiation marker (ß3-tubulin) and the cell adhesive molecule (integrin-ß1) with the existence of NGF-SPIO-Au NPs, while SMF did not show these effects. The results imply that noninvasive DMF-stimulated NPs can regulate intracellular Ca2+ influx and enhance neuron differentiation and neuroregeneration rate.

Blood-brain barrier crossing using magnetic stimulated nanoparticles.

Due to the low permeability and high selectivity of the blood-brain barrier (BBB), existing brain therapeutic technologies are limited by the inefficient BBB crossing of conventional drugs. Magnetic nanoparticles (MNPs) have shown great potential as nano-carriers for efficient BBB crossing under the external static magnetic field (SMF). To quantify the impact of SMF on MNPs' in vivo dynamics towards BBB crossing, we developed a physiologically based pharmacokinetic (PBPK) model for intraperitoneal (IP) injected superparamagnetic iron oxide nanoparticles coated by gold and conjugated with poly (ethylene glycol) (PEG) (SPIO-Au-PEG NPs) in mice. Unlike most reported PBPK models that ignore brain permeability, we first obtained the brain permeabilities with and without SMF by determining the concentration of SPIO-Au-PEG NPs in the cerebral blood and brain tissue. This concentration in the brain was simulated by the advection-diffusion equations and was numerically solved in COMSOL Multiphysics. The results from the PBPK model after incorporating the brain permeability showed a good agreement (regression coefficient R2 = 0.848) with the in vivo results, verifying the capability of using the proposed PBPK model to predict the in vivo biodistribution of SPIO-Au-PEG NPs under the exposure to SMF. Furthermore, the in vivo results revealed that the distribution coefficient from blood to brain under the exposure to SMF (4.01%) is slightly better than the control group (3.68%). In addition, the modification of SPIO-Au-PEG NPs with insulin (SPIO-Au-PEG-insulin) showed an improvement of the brain bioavailability by 24.47% in comparison to the non-insulin group. With the SMF stimulation, the brain bioavailability of SPIO-Au-PEG-insulin was further improved by 3.91% compared to the group without SMF. The PBPK model and in vivo validation in this paper lay a solid foundation for future study on non-invasive targeted drug delivery to the brain.

Surface imprinted polymer on a metal-organic framework for rapid and highly selective adsorption of sulfamethoxazole in environmental samples.

The demand for the removal of pollutants in aqueous solution has triggered extensive studies to optimize the performance of adsorbents, but the adsorption rate and selectivity of adsorbents have been overlooked. Hierarchically ordered porous vinyl-functionalized UIO-66 was used as supporter to prepare a surface molecular imprinted polymer (MIP-IL@UIO-66). The UIO-66 with large specific surface area significantly increased the number of active site of polymer, and so the MIP-IL@UIO-66 can achieve the rapid and highly selective adsorption of sulfamethoxazole (SMZ) in water. The structure and morphology of MIP-IL@UIO-66 was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, nitrogen adsorption-desorption isotherms, thermogravimetry, X-ray photoelectron spectroscopy, and X-ray powder diffraction. Results indicate that the presented MIP-IL@UIO-66 has an ultrafast equilibrium rate (equilibrium time, 10 min), large adsorption capability (maximum capacity, 284.66 mg g-1), excellent adsorption selectivity (selectivity coefficient, 11.36), and good reusability (number of cycles, 5 times) via equilibrium adsorption experiments. Subsequently, as a novel solid phase extraction (SPE) adsorbent, the adsorption performance of SMZ onto MIP-IL@UIO-66 was better than that of a commercial SPE adsorbent. A MISPE column combined with high-performance liquid chromatography (HPLC) was presented to detect SMZ in water, soil, egg, and pork samples with recoveries of 91-106%. Hydrogen bonds, electrostatic and π-π interactions, and molecular memory were attributed to recognizing the SMZ of MIP-IL@UIO-66.

Eco-friendly ionic liquid imprinted polymer based on a green synthesis strategy for highly selective adsorption tylosin in animal muscle samples.

A novel eco-friendly molecularly imprinted polymer (MIP) was proposed as solid-phase extraction (SPE) adsorbent to selective adsorption tylosin (TYL) in animal muscle samples. The MIP was synthesized in aqueous by using 1,4-butanediyl-3,3-bis-1-vinyl imidazolium chloride and 2-acrylamide-2-methylpropanesulfonic acid as bifunctional monomer. The obtained MIP had excellent selectivity towards TYL in water, and the maximum binding capacity can reach 123.45 mg g-1. Combined with high-performance liquid chromatography, the presented MIP can be used as SPE sorbent to recognize and detect TYL in the range of 0.008 to 0.6 mg L-1 (R2 = 0.9995). The limit of detection and limit of quantification were 0.003 mg L-1 and 0.008 mg L-1, and the intraday and interday precision were 1.05% and 3.36%, respectively. Under the optimal condition, the established MIP-SPE-HPLC method was successfully applied to separate and determine trace TYL in chicken, pork, and beef samples with satisfactory recoveries ranged from 94.0 to 106.3%, and the MIP-SPE cartridge can be cycled at least 20 times. This study implies a promising green MIP-SPE-HPLC method for highly selective adsorption and analysis trace TYL in complex matrices.

Personalized dynamic transport of magnetic nanorobots inside the brain vasculature.

Delivering specific bioactive agents with sufficient bioavailability to the targeted brain area across blood brain barrier remains a big challenge. Magnetically driven nanorobots have demonstrated their potential for controlled drug delivery. However, the dynamic transport of these nanorobots inside each individual's brain vasculature is not yet well studied. Addressing this is a critical step forward to controlled drug delivery for non-invasive brain therapeutics. In this paper, we develop an analytical model describing the personalized dynamic transport of spherical magnetic nanorobots inside the brain vasculature reconstructed from the patient's angiography images. By inverting the transporting process, we first design the patient-specific transport path based on the reconstructed vascular model, and then calculate the magnetic force required to drive these nanorobots from the analytical model. Also, a finite element model is created to simulate the inverse design process, which implies that the delivery efficiency of these magnetically driven nanorobots to the targeted brain area can be increased by 20% and almost 95% nanorobots arrive at the desired vessel walls. In the end, a simplified brain vascular model is printed using PolyJet 3D 750 to demonstrate the dynamic transport of these nanorobots toward the targeted site. The proposed theoretical modeling, numerical simulation and experimental validation lay solid foundation toward non-invasive brain therapeutics with maximal accuracy and minimal side effects.

Molecular mechanism and role of microRNA-93 in human cancers: A study based on bioinformatics analysis, meta-analysis, and quantitative polymerase chain reaction validation.

INTRODUCTION: Currently, studies have shown that microRNA-93 (miR-93) can be an oncogene or a tumor suppressor in different kinds of cancers. The role of miR-93 in human cancers is inconsistent and the underlying mechanism on the aberrant expression of miR-93 is complicated. METHODS: We first conducted gene enrichment analysis to give insight into the prospective mechanism of miR-93. Second, we performed a meta-analysis to evaluate the clinical value of miR-93. Finally, a validation test based on quantitative polymerase chain reaction (qPCR) was performed to further investigate the role of miR-93 in pan-cancer. RESULTS: Gene Ontology (GO) enrichment analysis results showed that the target genes of miR-93 were closely related to transcription, and MAPK1, RBBP7 and Smad7 became the hub genes. In the diagnostic meta-analysis, the overall sensitivity, specificity, and area under the curve were 0.76 (0.64-0.85), 0.82 (0.64-0.92), and 0.85 (0.82-0.88), respectively, which suggested that miR-93 had excellent performance on the diagnosis for human cancers. In the prognostic meta-analysis, dysregulated miR-93 was found to be associated with poor OS in cancer patients. In the qPCR validation test, the serum levels of miR-93 were upregulated in breast cancer, breast hyperplasia, lung cancer, chronic obstructive pulmonary disease, nasopharyngeal cancer, hepatocellular cancer, gastric ulcer, endometrial cancer, esophageal cancer, laryngeal cancer, and prostate cancer compared with healthy controls. CONCLUSIONS: miR-93 could act as an effective diagnostic and prognostic factor for cancer patients. Its clinical value for cancer early diagnosis and survival prediction is promising.

sTLR4/MD-2 complex inhibits colorectal cancer migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

Long non-coding RNAs (lncRNAs) have multiple functions in gene regulation and during cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) have not yet been well understood. In our previous study, we demonstrated that sTLR4/MD-2 complex can inhibit CRC in vitro and in vivo by targeting LPS. Therefore, the aim of the present study is to investigate the expression of lncRNA H19 in CRC and to evaluate its effect on the inhibition of sTLR4/MD-2 complex. The expression of H19 is measured in 63 CRC tumor tissues and adjacent normal tissues by quantitative real-time PCR (qRT-PCR). The effects of H19 on migration and invasiveness are evaluated by wound healing assay, migration and invasion assays. Results showed that H19 is significantly overexpressed in cancerous tissues and CRC cell lines compared with adjacent normal tissues and a normal human intestinal epithelial cell line. Moreover, H19 overexpression is closely associated with CRC patients. Our in vitro data indicated that knockdown of H19 inhibits the migration and invasiveness of CRC cells. And in vivo sTLR4/MD-2 complex inhibits tumor growth in mice and the expression of H19 is down-regulated. These results suggest that sTLR4/MD-2 complex inhibits CRC migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

Evaluation on the diagnostic and prognostic values of long non-coding RNA BLACAT1 in common types of human cancer.

A growing number of evidence has indicated that long non-coding RNAs (lncRNA) may have many functions in the development and progression of cancer, and cloud serve as good diagnostic and prognostic biomarkers in cancers. However, these studies often revealed the changes of lncRNAs within a specific cancer type. Here, we focused on BLACAT1 and provided a comprehensive pan-cancer analysis to evaluate the diagnostic and prognostic values of BLACAT1. The expression data of BLACAT1 were came from the quantitative real-time polymerase chain reaction (qRT-PCR) and The Cancer Genome Atlas (TCGA) database, respectively. Our results showed that the change of serum BLACAT1 expression was similar to those in matched tissues. The expression level of BLACAT1 both in serum and tissues in multiple cancer types were significantly upregulated compared to those of matched non-cancer participants. The serum BLACAT1 had a high diagnostic performance among these 12 types of cancer. The relative AUC of serum BLACAT1 in cancer patients ranged from 0.833 to 0.967 compared to that in healthy subjects. Surprisingly, Kaplan-Meier survival analysis revealed that the high expression level of BLACAT1 was significantly associated with poor overall survival only in uterine corpus endometrial carcinoma (p = 0.002, log-rank test). These findings demonstrated that BLACAT1 could act as a non-specific diagnostic biomarker for cancers and a potential biomarker for prognosis prediction of endometrial cancer.

Meta-signature LncRNAs serve as novel biomarkers for colorectal cancer: integrated bioinformatics analysis, experimental validation and diagnostic evaluation.

The aim of this study is to explore the differentially expressed lncRNAs, which may have potential biological function and diagnostic value in colorectal cancer (CRC). Through integrated data mining, we finally identified nine differentially expressed lncRNAs and their potential mRNA targets. After a series of bioinformatics analyses, we screened significant pathways and GO terms that are related to the up-regulated and down-regulated transcripts respectively. Meanwhile, the nine lncRNAs were validated in 30 paired tissues and cell lines by qRT-PCR and the results were basically consistent with the microarray data. We also tested the nine lncRNAs in the serum of 30 CRC patients matched with the CRC tissue, 30 non-cancer patients and 30 health controls. Finally, we found that BLACAT1 was significant for the diagnosis of CRC. The area under the curve (AUC), sensitivity and specificity were 0.858 (95% CI: 0.765-0.951), 83.3% and 76.7% respectively between CRC patients and health controls. Moreover, BLACAT1 also had distinct value to discriminate CRC from other non-cancer diseases. The results indicated that the differentially expressed lncRNAs and their potential target transcripts could be considered as potential therapeutic targets for CRC patients. Meanwhile, lncRNA BLACAT1 might represent a new supplementary biomarker for the diagnosis of CRC.

Diagnostic accuracy of osteopontin plus alpha-fetoprotein in the hepatocellular carcinoma: A meta-analysis.

OBJECTIVE: Osteopontin (OPN) has been reported as a potential biomarker for diagnosis of hepatocellular carcinoma (HCC) in many inconsistent results. This study demonstrates a systematic meta-analysis for the evaluation on diagnostic accuracy of serum or plasma OPN and alpha-fetoprotein (AFP) alone and combined assays for HCC. METHODS: Relevant literatures were searched in PubMed up to August 2016. The quality of each study was evaluated by QUADAS-2 (quality assessment for studies of diagnostic accuracy). Statistical analysis was performed by Meta-Disc 1.4 and Stata 12.0. The random-effect models were used to estimate pooled sensitivity, specificity and other diagnostic indicators of OPN and/or AFP in HCC. RESULTS: A total of 14 case-control literatures (15 studies) met the inclusion criteria in this meta-analysis. The respective pooled diagnostic sensitivity and specificity were 0.71 (95% CI: 0.69-0.74) and 0.80 (95% CI: 0.78-0.82) for OPN; 0.61 (95% CI: 0.58-0.63) and 0.92 (95% CI: 0.91-0.94) for AFP; 0.82 (95% CI: 0.79-0.84) and 0.77 (95% CI: 0.74-0.80) for OPN plus AFP. Their area under the curve (AUC) values were 0.8786, 0.8718 and 0.9005, respectively. CONCLUSION: Combination of OPN and AFP was better than OPN or AFP alone in diagnosis of HCC.

[Risk factors associated with anastomotic leak in patients with Crohn disease undergoing bowel resections].

OBJECTIVE: To investigate the risk factors and the prevention management of anastomotic leak in patients with Crohn disease undergoing bowel resections. METHODS: Clinical data of 91 patients with Crohn disease undergoing intestinal resection from 1990 to 2010 were analyzed retrospectively. Logistic regression analysis was used to assess the risk factors of anastomotic leak. RESULTS: A total of 120 intestinal anastomosis were performed in 91 patients, and anastomosis leak occurred in 14 patients (11.7%). Univariate analysis showed that operative timing (emergency or elective surgery), anastomosis type (side-to-side or end to end and end-to-side), operative time (≥3 h or <3 h), methods of anastomosis (handsewn or stapled) were the risk factors for anastomotic leak (P<0.05). Multivariate analysis revealed that emergency surgery (OR=3.891, 95%CI:1.332-13.692), end to end and end-to-side anastomosis (OR=3.236, 95%CI:1.165-11.950), handsewn anastomosis (OR=5.715, 95%CI:1.454-17.328) were independent risk factors of anastomotic leak. CONCLUSION: Avoiding emergency operation, use of side to side anastomosis, and application of stapling may lower the incidence of postoperative anastomotic leak in patients with Crohn disease undergoing bowel resections.