MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage

1. Download : Download high-res image (188KB)
2. Download : Download full-size image

     

基于“整体观”探讨中药的研究思维和方法

中药源于自然，治疗疾病有自身的优势和特点，其作用方式一直是中药研究者们不断研究和探索的重要内容。本文从中医的“整体观”对中药起效机制进行深入思考，认为中药成分多样可契合生物多靶，而生物靶标之间的协同作用是中药起效机制的重要补充；此外，中药对情志及肠道菌群稳态的调节作用也不容忽视，或许可为今后开展中药作用机制的研究提供新的思维和方法。     

Prenylated phenolics as promising candidates for combination antibacterial therapy: Morusin and kuwanon G

Combination of antibiotics with natural products is a promising strategy for potentiating antibiotic activity and overcoming antibiotic resistance. The purpose of the present study was to investigate whether morusin and kuwanon G, prenylated phenolics in Morus species, have the ability to enhance antibiotic activity and reverse antibiotic resistance in Staphylococcus aureus and Staphylococcus epidermidis. Commonly used antibiotics (oxacillin, erythromycin, gentamicin, ciprofloxacin, tetracycline, clindamycin) were selected for the combination studies. Checkerboard and time-kill assays were used to investigate potential bacteriostatic and bactericidal synergistic interactions, respectively between morusin or kuwanon G and antibiotics. According to both fractional inhibitory concentration index and response surface models, twenty combinations (14 morusin-antibiotic combinations, six kuwanon G-antibiotic combinations) displaying bacteriostatic synergy were identified, with 4–512-fold reduction in the minimum inhibitory concentration values of antibiotics in combination. Both morusin and kuwanon G reversed oxacillin resistance of methicillin-resistant Staphylococcus aureus. In addition, morusin reversed tetracycline resistance of Staphylococcus epidermidis. At half of the minimum inhibitory concentrations, combinations of morusin with oxacillin or gentamicin showed bactericidal synergy against methicillin-resistant Staphylococcus aureus. Fluorescence and differential interference contrast microscopy and scanning electron microscopy showed an increase in the membrane permeability and massive leakage of cellular content in methicillin-resistant Staphylococcus aureus exposed to morusin or kuwanon G. Overall, our findings strongly indicate that both prenylated compounds are good candidates for the development of novel antibacterial combination therapies.     

雷公藤减毒研究进展

雷公藤为治疗类风湿性关节炎常用中药,具有清热解毒,祛风除湿,消肿止痛,杀虫止痒的功用,现代药理研究表明其具有抗炎、镇痛、抗肿瘤及免疫调节等作用,临床主要用于治疗免疫性疾病、肾脏性疾病、皮肤性疾病等,对类风湿性关节炎的疗效尤为显著。但严重的毒副作用,尤其是肝肾毒性,限制了其临床应用,成为迫切需要解决的难题,故雷公藤的减毒研究成为近年来的研究热点。本课题组主要研究雷公藤的经皮给药对其减毒增效的作用,但目前雷公藤的应用困境仍然没有得到改善,故对2006年至2016年近10年来雷公藤减毒研究的相关文献进行检索,包括传统的炮制减毒、配伍减毒和现代的制剂减毒、结构修饰减毒、生物技术减毒以及其相互的联合应用等,分析雷公藤的减毒现状和困境,对比现存减毒方式间的差异,为雷公藤减毒增效研究提供思路,促进其合理开发和临床安全应用,也为其他有毒中药的合理应用提供参考。     

Synergy between Tannerella forsythia and Fusobacterium nucleatum in biofilm formation

During dental plaque formation, the interaction of different organisms is important in the development of complex communities. Fusobacterium nucleatum is considered a 'bridge-organism' that facilitates colonization of other bacteria by coaggregation-mediated mechanisms and possibly by making the environment conducive for oxygen intolerant anaerobes. These studies were carried out to determine whether coaggregation between F. nucleatum and Tannerella forsythia is important in the formation of mixed species biofilms. Further, the role of BspA protein, a surface adhesin of T. forsythia, in coaggregation and biofilm formation was investigated. The results showed the development of synergistic mixed biofilms of F. nucleatum and T. forsythia when these bacteria were cocultured. The BspA protein was not involved in biofilm formation. Though BspA plays a role in coaggregation with F. nucleatum, presumably other adhesins are also involved. The synergistic biofilm formation between the two species was dependent on cell-cell contact and soluble components of the bacteria were not required. This study demonstrates that there is a positive synergy between F. nucleatum and T. forsythia in the development of mixed biofilms and that the cell-cell interaction is essential for this phenomenon.     

Innocent until proven guilty: mechanisms and roles of Streptococcus–Candida interactions in oral health and disease

Candida albicans and streptococci of the mitis group colonize the oral cavities of the majority of healthy humans. While C. albicans is considered an opportunistic pathogen, streptococci of this group are broadly considered avirulent or even beneficial organisms. However, recent evidence suggests that multi‐species biofilms with these organisms may play detrimental roles in host homeostasis and may promote infection. In this review we summarize the literature on molecular interactions between members of this streptococcal group and C. albicans, with emphasis on their potential role in the pathogenesis of opportunistic oral mucosal infections.     

Enhanced efficacy of imipenem-colistin combination therapy against multiple-drug-resistant Enterobacter cloacae: in vitro activity and a Galleria mellonella model

Background/Purpose

To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further.

Translational Study Searching for Synergy between Glycopyrronium and Indacaterol

We aimed to explore whether the acute bronchodilation induced by indacaterol 150 μg and glycopyrronium bromide 50 μg is additive or synergistic with respect to monocomponents by testing the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. Both indacaterol and glycopyrronium caused a concentration-dependent relaxation of human isolated bronchial tissues sub-maximally pre-contracted with acetylcholine; glycopyrronium was significantly more potent than indacaterol. The analysis of data using the Bliss Independence (BI) criterion indicated that glycopyrronium plus indacaterol produced an additive interaction at the isoeffective concentrations inducing EC₂₀ and a significant synergistic relaxant effect at isoeffective concentrations inducing EC₃₀. In COPD patients, the inhalation of indacaterol and glycopyrronium in combination significantly anticipated at 15 min post-administration the mean peak of bronchodilatory effect compared to the two drugs administered alone. The study of interaction between indacaterol and glycopyrronium by BI analysis evidenced an additive effect for FEV₁ between 5 min and 180 min post-inhalation, with synergistic interaction at 15 min post-administration, compared to the bronchodilation induced by these drugs administered alone. This study suggests that the combination ensures a broncholytic effect that is greater than that induced by the single monocomponents.