In vitro evidence of baicalein’s inhibition of the metabolism of zidovudine (AZT)

Background: Herb-drug interaction (HDI) has been regarded as a key factor limiting the clinical application of herbs and drugs. Aims: Potential baicalein-zidovudine (AZT) interaction was predicted in the present study. Methods: In vitro evaluation of baicalein’s inhibition towards human liver microsomes (HLMs)-catalyzed metabolism of zidovudine (AZT) was performed. Dixon and Lineweaver-Burk plots were used to determine the inhibition kinetic type, and second plot with the slopes from Lineweaver-Burk plot versus the concentrations of baicalein was employed to calculate the inhibition parameter (Ki). In combination with the in vivo concentration of baicalein, in vitro-in vivo extrapolation (IVIVE) was carried out to predict in vivo baicalein-AZT interaction. Results: Competitive inhibition of baicalein towards AZT metabolism was demonstrated, and the Ki value was calculated to be 101.2 μM. The value of AUCi/AUC was calculated to be 2. Conclusion: Potential baicalein-AZT interaction was indicated in the present study, indicating the need for monitoring when AZT is co-administrated with baicalein or baicalein-containing herbs.Keywords: Baicalein, zidovudine (AZT), metabolism, herb-drug interactionAfrican Health sciences Vol 14 No. 1 March 201

Molecular Analysis of Spring Viraemia of Carp Virus in China: A Fatal Aquatic Viral Disease that Might Spread in East Asian

Spring viraemia of carp (SVC) is a fatal viral disease for cyprinid fish, which is caused by spring viraemia of carp virus (SVCV). To date, no SVC outbreak has been reported in China. Between 1998 and 2002, outbreaks of SVC were reported in ornamental and wild fish in Europe and America, imported from multiple sources including China. Based on phylogenetic analysis, the viral strain isolated from America was shown to be originated from Asia. These outbreaks not only resulted in huge economic losses, but also raise an interesting question as to whether SVCV really exists in China and if so, is it responsible for SVC outbreaks? From 2002 to 2006, we screened 6700 samples from ornamental fish farms using the cell culture method of the Office International des Epizooties (OIE), and further verified the presence of SVCV by ELISA and real-time quantitative RT-PCR. Two infected samples were found and the complete genome of SVCV was sequenced from one of the isolates, termed SVCV-C1. Several unique hallmarks of SVCV-C1 were identified, including six amino acid (KSLANA) insertion in the viral RNA-dependent RNA polymerase (L) protein and ten nucleotide insertion in the region between glycoprotein (G) and L genes in European SVCV strains. Phylogenetic tree analysis of the full-length G protein of selected SVCV isolates from the United Kingdom and United States revealed that G proteins could be classified into Ia and Id sub genogroups. The Ia sub genogroup can be further divided into newly defined sub genogroups Ia-A and Ia-B. The isolates derived from the United States and China including the SVCV-C1 belongs to in the Ia-A sub genogroup. The SVCV-C1 G protein shares more than 99% homology with the G proteins of the SVCV strains from England and the United States, making it difficult to compare their pathogenicity. Comparison of the predicted three-dimensional structure based on the published G protein sequences from five SVCV strains revealed that the main differences were in the loops of the pleckstrin homology domains. Since SVCV is highly pathogenic, we speculate that SVC may therefore pose a serious threat to farmed cyprinid fish in China

c-Jun NH2-terminal kinase activation is essential for up-regulation of LC3 during ceramide-induced autophagy in human nasopharyngeal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Autophagy is a dynamic catabolic process characterized by the formation of double membrane vacuoles termed autophagosomes. LC3, a homologue of yeast Atg8, takes part in autophagosome formation, but the exact regulation mechanism of LC3 still needs to be elucidated.</p> <p>Methods</p> <p>Ceramide-induced autophagy was determined by detecting LC3 expression with Western blotting and confocal microscopy in human nasopharyngeal carcinoma cell lines CNE2 and SUNE1. The activation of JNK pathway was assessed by Western blotting for phospho-specific forms of JNK and c-Jun. The JNK activity specific inhibitor, SP600125, and siRNA directed against JNK were used to block JNK/c-Jun pathway. ChIP and luciferase reporter analysis were applied to determine whether c-Jun was involved in the regulation of LC3 transcription.</p> <p>Results</p> <p>Ceramide-treated cells exhibited the characteristics of autophagy and JNK pathway activation. Inhibition of JNK pathway could block the ceramide-induced autophagy and the up-regulation of LC3 expression. Transcription factor c-Jun was involved in LC3 transcription regulation in response to ceramide treatment.</p> <p>Conclusions</p> <p>Ceramide could induce autophagy in human nasopharyngeal carcinoma cells, and activation of JNK pathway was involved in ceramide-induced autophagy and LC3 expression.</p

The Fumigating Activity of Litsea cubeba oil and Citral on Solenopsis invicta

This paper studied the fumigating activity of Litsea cubeba oil and citral on Solenopsis invicta, identified and analyzed the chemical constituents and volatile components of L. cubeba oil via solid-phase microextraction which were then identified via gas chromatography-mass spectrometry. The results showed that citral and (z)-3,7-dimethylocta-2,6-diena were the main components of L. cubeba oil, as well as its volatile compounds. According to the experimental results, L. cubeba oil and citral had good fumigating activity on workers, and also had significant inhibition on the walking ability and climbing ability of workers. At the same time, the effects of the two agentia on the fumigating activity and behavioral inhibition of microergate were stronger than those of macroergate. After treating with L. cubeba oil and citral for 24 hours, the walking rate and grasping rate of microergate were both 0 %. The results showed that L. cubeba oil and citral had good control effect on S. invicta

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.</p> <p>Purpose</p> <p>To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.</p> <p>Methods</p> <p>45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.</p> <p>Results</p> <p>Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).</p> <p>Conclusions</p> <p>Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.</p

MKPM: Multi keyword-pair matching for natural language sentences

Sentence matching is widely used in various natural language tasks, such as natural language inference, paraphrase identification and question answering. For these tasks, we need to understand the logical and semantic relationship between two sentences. Most current methods use all information within a sentence to build a model and hence determine its relationship to another sentence. However, the information contained in some sentences may cause redundancy or introduce noise, impeding the performance of the model. Therefore, we propose a sentence matching method based on multi keyword-pair matching (MKPM), which uses keyword pairs in two sentences to represent the semantic relationship between them, avoiding the interference of redundancy and noise. Specifically, we first propose a sentence-pair-based attention mechanism sp-attention to select the most important word pair from the two sentences as a keyword pair, and then propose a Bi-task architecture to model the semantic information of these keyword pairs. The Bi-task architecture is as follows: 1. In order to understand the semantic relationship at the word level between two sentences, we design a word-pair task (WP-Task), which uses these keyword pairs to complete sentence matching independently. 2. We design a sentence-pair task (SP-Task) to understand the sentence level semantic relationship between the two sentences by sentence denoising. Through the integration of the two tasks, our model can understand sentences more accurately from the two granularities of word and sentence. Experimental results show that our model can achieve state-of-the-art performance in several tasks. Our source code is publicly availabl

Interleukin-17A Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Cardiomyocyte Apoptosis and Neutrophil Infiltration

ObjectivesThis study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms.BackgroundInflammatory processes play a major role in myocardial I/R injury. We recently identified IL-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown.MethodsThe involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetic deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro.ResultsInterleukin-17A was elevated after murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes but not CD4+ helper T cells were a major source of IL-17A. Anti–IL-17A monoclonal antibody treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels, and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. In contrast, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule-1 expression.ConclusionsIL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration

Early Prediction of Gestational Diabetes Mellitus in the Chinese Population via Advanced Machine Learning

Acknowledgments We thank all those who helped to collect the data and the graduate students who took part in the statistical analysis. Financial Support: This work was supported by the National Key Research and Development Program of China (grant Nos.2018YFC1002804 and 2016YFC1000203), the National Natural Science Foundation of China (grant Nos. 81671412 and 81661128010), Program of Shanghai Academic Research Leader (grant No. 20XD1424100), the Outstanding Youth Medical Talents of Shanghai Rising Stars of Medical Talent Youth Development Program, Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (grant No. 2019-12M-5-064), the Foundation of Shanghai Municipal Commission of Health and Family Planning (grant No. 20144Y0110), the Natural Science Foundation of Shanghai (grant Nos. 20511101900 and 20ZR1427200), the Shanghai Shenkang Hospital Development Center, the Clinical Technology Innovation Project (grant Nos. SHDC12019107), and the Clinical Skills Improvement Foundation of Shanghai Jiaotong University School of Medicine (grant No. JQ201717).Peer reviewedPublisher PD