The antiviral effect and potential mechanism of Houttuynia cordata thunb. (HC) against coxsackievirus A4.

ETHNOPHARMACOLOGICAL RELEVANCE: Hand, foot, and mouth disease (HFMD) is mainly caused by various of enteroviruses such as enterovirus 71 (EVA71), coxsackievirus A16 (CVA16), CVA6, and CVA10 in infants and children under 5 years old. During the past 5 years, CVA4 has become the dominant pathogen resulting in HFMD in China. However, there are no effective vaccines and antiviral drugs available. Houttuynia cordata Thunb (HC). is a Chinese herbal medicine eaten as vegetables for treating viral infection diseases, but whether HC has anti-CVA4 effect remains unclear. AIM OF THE STUDY: In this study, we want to investigate the antiviral activity of HC against CVA4 in vitro and in vivo and elucidate the potential mechanism of HC against CVA4. MATERIALS AND METHODS: MTT assay were used to evaluate the cytotoxicity of HC. Virus titers assay, CPE assay, violet staining and immunofluorescence were used to investigate the antiviral effect of HC against CVA4. A 13-day-old suckling mice model was established to evaluate the therapeutic efficacy of HC against CVA4 infection. Western blot, qRT-PCR and time-of-drug addition assay were performed to elucidate the potential mechanism of HC against CVA4 infection. RESULTS: MTT assay indicated the cytotoxicity concentration of HC on Vero cells and RD cells were more than 1 mg/ml, suggesting that the low cytotoxicity of HC. In vitro antiviral assay revealed that HC could dose-dependently prevent the CPE, suppress the release of newborn virus, and inhibit the replication of CVA4 by decreasing viral RNA transcription and protein expression with IC50 of 88.96 µg/mL. A time-of-addition assay showed that HC mainly exerted anti-CVA4 effect by inhibiting virus replication at the post-entry stage. In vivo results further demonstrated that HC could effectively prevent the lethal infection of CVA4 by promoting survival, improving clinical symptoms, prolonging the survival time, inhibiting excessive inflammatory responses, and reducing pathological injury in vivo. Mechanistic studies revealed inhibition of p38 MAPK and JNK pathway over-activation may be the primary mechanism of HC against CVA4 infection. CONCLUSION: In summary, our results for the first time demonstrated that HC not only effectively inhibited CVA4 replication, but also partially protected the lethal infection of CVA4 in vivo. Furthermore, pharmacological mechanism studies revealed that the primary mechanism of HC against CVA4 infection may be associated with its effect of inhibiting over-activation of p38 MAPK and JNK signaling pathways caused by enteroviruses. Our finding indicated that HC might be a potential innovative medicine for treating HFMD.

Virtual sketching-based dental anatomy module improves learners' abilities to use computer-aided design to create dental restorations and prostheses.

Dental anatomy education for dental technology students should be developed in alignment with digital dental laboratory practices. We hypothesized that a virtually assisted sketching-based dental anatomy teaching module could improve students' acquisition of skills essential for digital restoration design. The second-year dental technology curriculum included a novel virtual technology-assisted sketching-based module for dental anatomy education. Pre- and post-course assessments evaluated students' skill sets and knowledge bases. Computer-aided design (CAD) scores were analyzed after one year to assess how the skills students developed through this module impacted their subsequent CAD performance. Participants who undertook the dental sketching-based teaching module demonstrated significantly improved theoretical knowledge of dental anatomy, dental aesthetic perception, and spatial reasoning skills. A partial least squares structural equation model indicated that the positive effects of this module on subsequent CAD performance were indirectly mediated by dental aesthetic perception, spatial reasoning, and practice time. A virtually assisted sketching-based dental anatomy teaching module significantly improved students' acquisition of skills and knowledge and positively mediated dental technology students' CAD performance.

Combining magnetic nanoparticle capture and poly-enzyme nanobead amplification for ultrasensitive detection and discrimination of DNA single nucleotide polymorphisms.

The development of ultrasensitive methods for detecting specific genes and discriminating single nucleotide polymorphisms (SNPs) is important for biomedical research and clinical disease diagnosis. Herein, we report an ultrasensitive approach for label-free detection and discrimination of a full-match target-DNA from its cancer related SNPs by combining magnetic nanoparticle (MNP) capture and poly-enzyme nanobead signal amplification. It uses a MNP linked capture-DNA and a biotinylated signal-DNA to sandwich the target followed by ligation to offer high SNP discrimination: only the perfect-match target-DNA yields a covalently linked biotinylated signal-DNA on the MNP surface for subsequent binding to a neutravidin-horseradish peroxidase conjugate (NAV-HRP) for signal amplification. The use of polymer nanobeads each tagged with thousands of copies of HRPs greatly improves the signal amplification power, allowing for direct, amplification-free quantification of low aM target-DNA over 6 orders of magnitude (0.001-1000 fM). Moreover, this sensor also offers excellent discrimination between the perfect-match gene and its cancer-related SNPs and can positively detect 1 fM perfect-match target-DNA in the presence of 100 fold excess of co-existing single-base mismatch targets. Furthermore, it works robustly in clinically relevant media (e.g. 10% human serum) and gives even higher SNP discrimination than that in clean buffers. This ultrasensitive DNA sensor appears to have excellent potential for rapid detection and diagnosis of genetic diseases.

Polymer degradation and drug delivery in PLGA-based drug-polymer applications: A review of experiments and theories.

Poly (lactic-co-glycolic acid) (PLGA) copolymers have been broadly used in controlled drug release applications. Because these polymers are biodegradable, they provide an attractive option for drug delivery vehicles. There are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA polymers and concurrent drug release kinetics. This work is intended to provide a comprehensive and collective review of the physicochemical and physiological factors that dictate the degradation behavior of PLGA polymers and drug release from contemporary PLGA-based drug-polymer products. In conjunction with the existing experimental results, analytical and numerical theories developed to predict drug release from PLGA-based polymers are summarized and correlated with the experimental observations. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1692-1716, 2017.

Mathematical modeling and finite element simulation of slow release of drugs using hydrogels as carriers with various drug concentration distributions.

In drug release systems using hydrogels as carriers, the presence of the polymer network will reduce the drug release rate, which can extend the release period. For a controlled-release process of drug, usually the ideal situation is to get a zero-order drug release rate. In this paper, the mathematical model of hydrogel swelling processes is constructed on the basis of a biphasic theory, and then an integrated equation that considers both water convection and drug diffusion phenomena is used to describe the drug release process. The effects of the initial drug concentration with nonuniform distributions along the radial direction of hydrogel carriers on the release of drugs are studied through simulating two-dimensional hydrogel swelling processes by means of the COMSOL Multiphysics software. The simulation results show that along with the hydrogel swelling, the drug release rate is changing, and the major influencing factors of the drug release rate are water convection and drug diffusion coefficient, which are affected by water volume fraction, drug concentration distribution in matrix, and carrier radius. The results also indicate that the initial drug concentration distribution following a sine curve can result in an ideal zero-order release process.