In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B−NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure−activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B−NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.KEY WORDS: Flavivirus, Zika virus, Dengue virus, Antiviral, Protease inhibitor, Erythrosin B     

Reimmunization of children immunized at 18 months of age with Haemophilus influenzae type b vaccine

We studied the response to reimmunization at 36 months of age with Haemophilus influenzae type b (Hib) polyribosylribitol phosphate (PRP) capsular polysaccharide vaccine. Children enrolled in the study had previously received PRP or PRP plus diphtheria and tetanus toxoids with pertussis vaccine at 18 months of age. A control group of children, who received a first dose at 36 months of age, was also studied. Ninety-five percent of children receiving a second dose of vaccine had a postimmunization anti-capsular antibody level of greater than or equal to 1 microgram/mL. In comparison, 70% of 36-month-old children who received their first dose of PRP had a postimmunization level greater than or equal to 1 microgram/mL (P = 0.09). The geometric mean titer at 37 months of age was 8.64 micrograms/mL in children who had received two doses of PRP vaccine, compared with 2.19 micrograms/mL in the group who received only one dose of PRP at 36 months of age (P = 0.04). We conclude that infants immunized at 17 to 19 months of age with PRP had an excellent immunologic response to reimmunization at 36 months of age.     

Triterpenoids and aromatics from Derris laxiflora

Seven new compounds, O-trans-cinnamoylglutinol (1), 22β-hydroxy-12-oleanen-3-one (2), 15α,16α-epoxy-12-oleanen-3-one (3), 29-hydroxy-12-oleanene-3,22-dione (4), 22β,29-dihyroxy-12-oleanen-3-one (5), 2,3-(methylenedioxy)-4-methoxy-5-methylphenol (8), and 2,3,6-trimethoxy-5-methylphenol (9), as well as two first isolated from natural sources, 25-cycloartene-3,24-dione (6) and 24ξ-hydroxy-25-cycloarten-3-one (7), were characterized from Derris laxiflora. The structures of these compounds were determined by analysis of their spectroscopic data.     

Anti-inflammatory cembranoids from the soft corals Sinularia querciformis and Sinularia granosa

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Mosher's method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.     

Maleimide and maleic anhydride derivatives from the mycelia of Antrodia cinnamomea and their nitric oxide inhibitory activities in macrophages

On cultivation of the fungus Antrodia cinnamomea (BCRC 36799) on a medium, the mycelium was extracted and evaluated for nitric oxide (NO) inhibitory activity. Bioactivity-directed fractionation led to the isolation of two new maleimide derivatives, antrocinnamomins A (1) and B (2), and two new maleic anhydride derivatives, antrocinnamomins C (3) and D (4), along with three known compounds, 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]furan-2,5-dione (5), 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrole-2,5-dione (6), and 3-isobutyl-4-[4-(3-methyl-2-butenyloxy)phenyl]-1H-pyrrol-1-ol-2,5-dione (7). Structural elucidation of compounds 1-4 was carried out by spectroscopic data. Compound 1 displayed significant inhibitory effect on nitric oxide (NO) production.     

Mining Health Social Media with Sentiment Analysis

With the rapid development of the Internet, more and more users utilize health communities (known as forums) to find health-related information, share their medical stories and experiences, or interact with other people in the communities. In this paper, we propose a framework to analyze the user-generated contents in a health community. The proposed framework contains three phases. First, we extract medical terms, including conditions, symptoms, treatments, effectiveness and side effects to form a virtual document for each question in the community. Next, we modify Latent Dirichlet Allocation (LDA) by adding a weighted scheme, called conLDA, to cluster virtual documents with similar medical term distributions into a conditional topic (C-topic). Finally, we analyze the clustered C-topics by sentiment polarities, and physiological and psychological sentiment. The experiment results show that conLDA outperforms the original LDA, and can cluster relevant medical terms and relevant questions together. The C-topics clustered by conLDA are more thematic than those clustered by the original LDA. The results of sentiment analysis may provide a quick reference and valuable insights for patients, caregivers and doctors.     

高糖对体外培养兔视网膜Müller细胞AQP4表达的影响

目的：观察体外培养兔视网膜Müller细胞在高糖条件下水通道蛋白-4（AQP4）表达的变化。方法：采用体外培养的兔视网膜Müller 细胞,分为正常对照组及高糖组（葡萄糖浓度：30、40和50 mmol•L^-1）,分别培养1、3和5 d;采用免疫细胞化学、流式细胞术及RT-PCR方法对Müller 细胞AQP4的表达情况进行检测。结果：高糖组Müller 细胞AQP4表达的绿色荧光明显弱于正常对照组（P<0.01）;流式细胞仪检测中波峰位置明显提前,AQP4表达强度较对照组明显减弱（P<0.01）,且随着葡萄糖浓度的增高和作用时间的延长,AQP4表达强度逐渐减弱;血糖浓度50 mmol•L^-1培养3 d时,RT-PCR半定量分析显示,AQP4 mRNA的表达比对照组明显降低（P<0.01）。结论：高糖能降低视网膜Müller细胞AQP4的表达,且随着葡萄糖浓度的增高和作用时间的延长,AQP4的表达强度也逐渐减弱;高糖时AQP4的表达下降可能是机体对糖尿病视网膜病变的一种保护性反应。