Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses.

Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 µM) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 ± 0.05 µM against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-ß response, since knockdown of IFN-ß abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg · kg-1 · d-1, i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-γ, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-ß by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.

Novel Biocompatible Polysaccharide-Based Eutectogels with Tunable Rheological, Thermal, and Mechanical Properties: The Role of Water.

The natural deep eutectic solvent (NADES) is an excellent solvent for insoluble natural products and medicines. Eutectogels formed by gelation of NADESs are interesting materials that deserve attention. In this study, xanthan gum was used as a gelator to gel choline chloride-xylitol with different water contents in virtue of the excellent solubility of choline chloride-xylitol (1:1) to quercetin. We observed that water was critical to the formation of eutectogels. An MTT assay indicated that our eutectogel had excellent biocompatibility as its corresponding hydrogel. According to rheological tests, xanthan gum-based eutectogels had better viscoelastic properties, higher thermal stability, and more defined shear thinning behavior than its corresponding hydrogel. Texture profile analysis showed that eutectogels with less water content had higher hardness and adhesiveness. Meanwhile, Differential scanning calorimeter (DSC) results suggested that the various rheological and texture properties of eutectogels could be attributed to changes in the water state, which was influenced by the hydrogen bonding network of NADES. This biocompatible eutectogel with tunable properties was expected to find applications in novel drug delivery vehicles, which are widely used in the fields of medicine and food.

Analysis of risk factors causing short-term cement leakages and long-term complications after percutaneous kyphoplasty for osteoporotic vertebral compression fractures.

Background Percutaneous kyphoplasty (PKP) is a common treatment modality for painful osteoporotic vertebral compression fractures (OVCFs). Pre- and postoperative identification of risk factors for cement leakage and follow-up complications would therefore be helpful but has not been systematically investigated. Purpose To evaluate pre- and postoperative risk factors for the occurrence of short-term cement leakages and long-term complications after PKP for OVCFs. Material and Methods A total of 283 vertebrae with PKP in 239 patients were investigated. Possible risk factors causing cement leakage and complications during follow-up periods were retrospectively assessed using multivariate analysis. Cement leakage in general, three fundamental leakage types, and complications during follow-up period were directly identified through postoperative computed tomography (CT). Results Generally, the presence of cortical disruption ( P = 0.001), large volume of cement ( P = 0.012), and low bone mineral density (BMD) ( P = 0.002) were three strong predictors for cement leakage. While the presence of intravertebral cleft and Schmorl nodes ( P = 0.045 and 0.025, respectively) were respectively identified as additional risk factors for paravertebral and intradiscal subtype of cortical (C-type) leakages. In terms of follow-up complications, occurrence of cortical leakage was a strong risk factor both for new VCFs ( P = 0.043) and for recompression ( P = 0.004). Conclusion The presence of cortical disruption, large volume of cement, and low BMD of treated level are general but strong predictors for cement leakage. The presence of intravertebral cleft and Schmorl nodes are additional risk factors for cortical leakage. During follow-up, the occurrence of C-type leakage is a strong risk factor, for both new VCFs and recompression.

Antineutrophil cytoplasmic antibody­associated vasculitis complicated with oral and maxillofacial space infection in a young woman: A case report.

Antibody-associated vasculitis (AAV) is a systemic autoimmune disease, with hormones and immunosuppressants as its main treatment measures. However, during the treatment process, various infections such as lung infections and urinary tract infections are prone to occur, and patients with OMSI are relatively rare. The present case report describes the case of a young woman who received long-term oral glucocorticoids and immunosuppressive agents for the treatment of antineutrophil cytoplasmic (AAV). At hospital admission, the patient with a high fever and painful swelling of the left side of the mouth. The patient was diagnosed with an oral and maxillofacial space infection (OMSI). Therefore, the local incision, drainage and irrigation of abscesses were subsequently performed. Additionally, the immunosuppressive agents were discontinued, the glucocorticoid dose was reduced and intravenous antibiotic therapy was provided. The patient was discharged 1 week later in good condition. Notably, the incidence of AAV is extremely low. Although OMSI is not uncommon, the simultaneous occurrence of AAV in combination with OMSI has not been reported previously. To the best of our knowledge, this is the first reported case of AAV combined with OMSI.

Combined effects of nanosized polystyrene and erythromycin on bacterial growth and resistance mutations in Escherichia coli.

Toxicological effects of nanoplastics have been demonstrated in a variety of organisms, yet their impacts on bacteria, especially on the antibiotic resistance evolution remain under explored. Herein, we report individual and combined effects of nano-polystyrene (nano-PS) and erythromycin (ERY) on growth and resistance mutations of Escherichia coli. The toxicity of nano-PS was dependent on size and functional modifications, with 30 nm and amino-modified PS (PS-NH2, 200 nm) showing the greatest toxicity. Adsorption of nano-PS onto bacterial surface and the subsequent increase of intracellular ROS or the probable mechanical damage were considered as the primary toxic mechanisms. Furthermore, nano-PS increased the bacterial resistance mutations, which was due to the oxidative damage to DNA and the SOS response. In addition, PS-NH2 presented synergistic effects with ERY while non-modified PS had no impact, although both of them showed adsorption capacity to ERY. This was likely because the positively charged PS-NH2 acted as a carrier of ERY and enhanced the interactions between ERY and the bacteria. Our findings raised the concerns about the risk of nanoplastics in accelerating the bacterial resistance evolution, and highlighted the necessity of including combined effects of nanoplastics and co-contaminants in risk assessment.

Evaluation of MR issues for the latest standard brands of orthopedic metal implants: plates and screws.

PURPOSE: The study was performed to evaluate magnetic resonance (MR) issues for the latest standard brands of plates and screws used in orthopedic surgery at a 1.5-T MR system, including the safety and metallic artifacts. METHODS: The plates and screws (made of titanium alloy and stainless steel materials, according to the latest standard brands) were assessed for displacement in degrees, MRI-related heating and artifacts at a 1.5-T MR system. The displacement in degrees of the plates and screws was evaluated on an angel-measurement instrument at the entrance of the MR scanner. The MRI-related heating was assessed on a swine leg fixed with a plate by using a "worst-case" pulse sequence. A rectangular water phantom was designed to evaluate metallic artifacts of a screw on different sequences (T1/T2-weighted FSE, STIR, T2-FSE fat saturation, GRE, DWI) and then artifacts were evaluated on T2-weighted FSE sequence by modifying the scanning parameters including field of view (FOV), echo train length (ETL) and bandwidth to identify the influence of parameters on metallic artifacts. 15 volunteers with internal vertebral fixation (titanium alloy materials) were scanned with MR using axial and sagittal T2-FSE, sagittal T2-FSE fat suppression and STIR with conventional and optimized parameters, respectively. Then all images were graded by two experienced radiologists having the experience of more than 7 years under double-blind studies that is neither of them knew which was conventional parameter group and optimized parameter group. RESULTS: The average deflection angle of titanium alloy and stainless steel implants were 4.3° and 7.7°, respectively, (less than 45°) which indicated that the magnetically induced force was less than the weight of the object. The deflection angle of the titanium alloy implants was less than the stainless steel one (t=9.69, P<0.001). The average temperature changes of titanium alloy before and after the scan was 0.48°C and stainless steel implants was 0.74°C, respectively, with the background temperature changes of 0.24°C. The water phantom test indicated that the DWI sequence produced largest artifacts, while FSE pulse sequence produced smallest artifacts. And T2-weighted FSE fat saturation sequence produced larger artifacts than STIR sequence. The influence of the scanning parameters on metallic artifacts was verified that metallic artifacts increased with longer echo train length and bigger FOV, while decreased with larger bandwidth. The interreader agreement was good or excellent for each set of images graded with Cohen's Kappa statistic. Image grading of axial and sagittal T2-FSE with optimized parameters were significantly superior to that with conventional parameters (grade, 3.3±0.5 vs 2.7±0.6, P=0.003; 3.2±0.4 vs 1.9±0.7, P=0.001) and image of STIR sequence received a better grade than T2-FSE FS sequence (grade, 3.4±0.5 vs 1.7±0.6, P<0.001). CONCLUSIONS: The latest standard plates and screws used in orthopedic surgery do not pose an additional hazard or risk to patients undergoing MR imaging at 1.5-T or less. Though artifacts caused by them cannot be ignored because of their relatively large size, it is possible to be minimized by choosing appropriate pulse sequences and optimizing scanning parameters, such as FSE and STIR sequence with large bandwidth, small FOV and appropriate echo train length.