The preparation of a boronate affinity-based controlled oriented imprinting coating on a silica nanoparticle surface for the separation and purification of shikimic acid in herbal medicine.

Shikimic acid (SA) is one of the most effective drugs against the A (H1N1) virus and has high medicinal value. Additionally, it has the ability to generate non-toxic herbicides and antimicrobial medications. The extraction from plants has proven to be the main route of production of SA with economic benefits and environmental efficiency. Therefore, it is necessary to perform purification of SA from these herbal medicines before quantifying it. In this study, researchers employed a boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) as highly effective solid phase extraction (SPE) adsorbents for the isolation and purification of SA. 3-Fluoro-4-formylphenylboronic acid functionalized silica nanoparticles were used as supporting materials for immobilizing SA. Poly(2-anilinoethanol) with a higher hydrophilic domain can be used as an effective imprinting coating. The prepared SA-imprinted silica nanoparticles exhibited several significant results, such as good specificity, high binding capacity (39.06 ± 2.24 mg g-1), moderate binding constant (6.61 × 10-4 M-1), fast kinetics (8 min) and low binding pH (pH 5.0) toward SA. The replication of SA-imprinted silica nanoparticles was deemed satisfactory. The SA-imprinted silica nanoparticles could be still reused after seven adsorption-desorption cycles, which indicated high chemical stability. In addition, the recoveries of the proposed method for SA at three spiked level analysis in star aniseed and meadow cranesbill were 96.2% to 109.0% and 91.6% to 103.5%, respectively. The SA-imprinted silica nanoparticles that have been prepared are capable of identifying the target SA in real herbal medicines. Our approach makes sample pre-preparation simple, fast, selective and efficient.

A ratiometric electrochemical strategy based on Fe (III) and Pt (IV) for immobilization-free detection of Escherichia coli.

A new ratiometric electrochemical strategy for immobilization-free detection of Escherichia coli (E. coli) was constructed by using a capture DNA-polyaniline/copper ferrite nanoparticles/graphene oxide (cDNA-PANI/CuFe2O4/GO) composite as capture probes, which has a high specific surface area and good magnetic properties. Then trigger DNA/Au nanoparticles (tDNA/Au NPs) were used as signal amplification labels, and Pt (IV) and Fe (III) were chosen as the signal probes. In the presence of targets, the sandwich format among cDNA-PANI/CuFe2O4/GO, E. coli and auxiliary DNA (aDNA) was realized by using the aptamer recognition system. Then, the tDNA/Au binding could be anchored on the sandwich format due to the principle of base complementation between unpaired aDNA and tDNA. And the unbounded tDNA of tDNA/Au NPs could bind an amount of Pt (IV). After separation using a magnet, a handful of unbound Pt (IV) which remained in the supernatant reacted with a large number of Fe (III) ions, leading to a markedly increased IFe(III)/IPt(IV) value. Oppositely, the sandwich format could not appear in the absence of targets, and even the tDNA/Au could not be immobilized on it. So, the redox reaction between a large amount of Pt (IV) residue in the supernatant and Fe (III) was significantly successful, causing a low IFe(III)/IPt(IV) value. Under optimal conditions, we found that IFe(III)/IPt(IV) was linearly related to the logarithmic E. coli concentration with a low limit of detection (1.862 × 103 cfu mL-1). This devised ratiometric electrochemical method may develop into a powerful and effective means for the detection of E. coli in real samples, which may also be developed as a universal tool for another microorganism.

Preoperative laser reduces silicone oil use in primary diabetic vitrectomy.

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

Licorice isoliquiritigenin-encapsulated mesoporous silica nanoparticles for osteoclast inhibition and bone loss prevention.

Mesoporous silica nanoparticles (MSNs) are extensively used in bone tissue regeneration and local drug delivery. However, the effects of MSNs alone on osteoclast formation and function, as well as the utilization of MSNs to deliver natural molecules against bone resorption, remain unexplored. Here, we report the development of licorice-derived bioactive flavonoid isoliquiritigenin (ISL)-encapsulated MSNs (MSNs-ISL) as a potent bone-bioresponsive nanoencapsulation system for prevention of osteoclast-mediated bone loss in vitro and in vivo. Methods: We synthesized MSNs-ISL and then investigated the drug loading and release characteristics of the resulting nanoparticles. In vitro experiments on osteoclast differentiation and bone resorption were performed using mouse primary bone marrow-derived macrophages (BMMs). In vivo animal experiments were conducted using a lipopolysaccharide (LPS)-mediated calvarial bone erosion model. Results: The resulting MSNs-ISL were spherical and highly monodispersed; they possessed a large specific surface area and superior biocompatibility, and allowed acid-sensitive sustained drug release. Compared with free ISL and MSNs alone, MSNs-ISL significantly and additively inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast generation, decreased the size and quantity of sealing zones, and reduced the osteolytic capacity of osteoclasts in vitro. MSNs-ISL treatment also downregulated RANKL-stimulated mRNA expression of osteoclast-associated genes and transcription factors. Mechanistically, MSNs-ISL remarkably attenuated the RANKL-initiated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of mitogen-activated protein kinases (MAPKs), and phosphorylation and degradation of inhibitor of κBα (IκBα), together with the nuclear translocation of nuclear factor-κB (NF-κB) p65 and the activator protein (AP)-1 component c-Fos. Moreover, MSNs-ISL almost completely restrained the expression of nuclear factor of activated T cells (NFATc1). Consistent with the in vitro results, MSNs-ISL could block osteoclast activity; relieve inflammation-related calvarial bone destruction in vivo; and suppress c-Fos, NFATc1, and cathepsin K expression levels. Conclusion: Licorice ISL-encapsulated MSNs exhibit notable anti-osteoclastogenetic effects and protect against inflammatory bone destruction. Our findings reveal the feasibility of applying MSNs-ISL as an effective natural product-based bone-bioresponsive nanoencapsulation system to prevent osteoclast-mediated bone loss.

Grape seed-derived procyanidins alleviate gout pain via NLRP3 inflammasome suppression.

BACKGROUND: Gout is one of the common inflammatory arthritis which affects many people for inflicting unbearable pain. Macrophage-mediated inflammation plays an important role in gout. The uptake of monosodium urate (MSU) crystals by macrophages can lead to activation of NOD-like receptors containing a PYD 3 (NLRP3) inflammasome, thus accelerating interleukin (IL)-1ß production. Reactive oxygen species (ROS) promoted development of the inflammatory process through NLRP3 inflammasome. Our study aimed to find a food-derived compound to attenuate gout pain via the specific inhibition of the NLRP3 inflammasome in macrophages. METHODS: CD-1 mice were used to evaluate the degree of pain and the swelling dimension of joints after an intra-articular (IA) MSU injection in the ankle. The murine macrophage cell line Raw 264.7 was used to investigate the effects of procyanidins and the mechanism underlying such effects. Histological analysis was used to measure the infiltration of inflammatory cells. ROS produced from Raw 264.7 cells were evaluated by flow cytometry. Cell signaling was measured by Western blot assay and immunofluorescence. RESULTS: Procyanidins significantly attenuated gout pain and suppressed ankle swelling. Procyanidins also inhibited MSU-induced activation of the NLRP3 inflammasome and increase of IL-1ß. Furthermore, procyanidins decreased ROS levels in Raw 264.7 cells. CONCLUSIONS: Suppression of the NLRP3 inflammasome in macrophages contributes to the amelioration of gout pain by procyanidins.

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization.

One of the key steps during tumour metastasis is tumour cell migration and invasion, which require actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are the filopodia, which act like cell sensory organs to communicate with the extracellular microenvironment and participate in fundamental cell functions such as cell adhesion, spreading and migration in the three-dimensional environment. Fascin is the main actin-bundling protein in filopodia. Using high-throughput screening, here we identify and characterize small molecules that inhibit the actin-bundling activity of fascin. Focusing on one such inhibitor, we demonstrate that it specifically blocks filopodial formation, tumour cell migration and invasion in vitro, and metastasis in vivo. Hence, target-specific anti-fascin agents have a therapeutic potential for cancer treatment.