Recent advances in bacteriophage-based therapeutics: Insight into the post-antibiotic era

Antibiotic resistance is one of the biggest threats to global health, as it can make the treatment of bacterial infections in humans difficult owing to their high incidence rate, mortality, and treatment costs. Bacteriophage, which constitutes a type of virus that can kill bacteria, is a promising alternative strategy against antibiotic-resistant bacterial infections. Although bacteriophage therapy was first used nearly a century ago, its development came to a standstill after introducing the antibiotics. Nowadays, with the rise in antibiotic resistance, bacteriophage therapy is in the spotlight again. As bacteriophage therapy is safe and has significant anti-bacterial activity, some specific types of bacteriophages (such as bacteriophage phiX174 and Pyo bacteriophage complex liquid) entered into phase III clinical trials. Herein, we review the key points of the antibiotic resistance crisis and illustrate the factors that support the renewal of bacteriophage applications. By summarizing recent state-of-the-art studies and clinical data on bacteriophage treatment, we introduced (i) the pharmacological mechanisms and advantages of antibacterial bacteriophages, (ii) bacteriophage preparations with clinical potential and bacteriophage-derived anti-bacterial treatment strategies, and (iii) bacteriophage therapeutics aimed at multiple infection types and infection-induced cancer treatments. Finally, we highlighted the challenges and critical perspectives of bacteriophage therapy for future clinical development.     

Recent advances in computer-aided drug design methods

A number of computational advances have had significant impact on the field of computer-aided drug design over the last several years. These advances can be grouped into three basic areas: conformational modelling (of small molecules, macromolecules and their complexes), property modelling (of physical, biological and chemical properties) and molecular design (to optimise physical, biological or chemical properties). The current state of the art in each of these areas is introduced. Recent patents related to these three topics are critically reviewed and their impact on the field of computer-aided drug design is assessed.     

核酸适配体药物生物分析方法的研究进展

目的结合目前核酸适配体药物的体内研究,综述核酸适配体药物的生物分析方法。方法查阅国内外近年相关文献42篇,对其进行归纳、总结,从核酸适配体药物研究概况、分析样品前预处理差异及各方法的优缺点等方面进行了介绍。结果应用于核酸适配体药物定量的生物分析方法各有其优缺点,应用时应根据具体情况合理选择灵敏度高、专属性强的方法。结论随着核酸适配体技术的发展,不断有崭新的核酸适配体药物诞生、完善、进入临床阶段并最终成为上市药物,针对其体内定性和定量的分析方法也将越来越成为研究热点。     

激活细菌沉默基因簇的研究进展

目的综述了近年来细菌沉默基因簇激活策略的研究进展。方法通过查阅文献对激活细菌沉默基因簇的研究进展进行了总结。结果微生物基因组序列的持续揭示表明,细菌在合成各种天然产物方面蕴藏着巨大的、尚未开发的潜能。一般来说,这些天然产物一直是药物先导化合物的重要来源。在标准的实验室条件下,大多数生物合成基因簇处于低表达或沉默状态。为此,我们回顾了近年来已开发的三种激活沉默生物合成基因簇的方法:使用CRISPR/Cas9插入活性启动子,高通量筛选激活剂用以鉴定小分子诱导剂,以及报告基因指导下的突变体筛选用以构建高产菌株。结论结合以前实施的策略,这些方法有望在未来几年内获得由这些沉默基因簇编码的天然产物。     

Eliminating pharmaceutical impurities: Recent advances in detection techniques

The elimination of organic impurities to produce highly pure drug substances is an important goal of process chemistry. For the detection of general impurities, hyphenated techniques (eg, liquid chromatography-mass spectrometry [LC-MS]) play a critical role in rapid structural identification (qualitative detection) and in understanding the mechanisms of formation of the impurities, enabling informed decisions to control and eliminate the impurities resulting from the chemical process where possible. Concern regarding genotoxic impurities (GTIs), which must typically be controlled at low parts-per-million limits, continues to increase, and significant advances have been achieved in recent years for the selective and sensitive quantitation (quantitative detection) of such impurities. Conventional detection techniques, such as ultraviolet (UV) detection, are often inadequate for the detection of potentially minute quantities of GTIs; therefore, various advanced MS-based detection strategies, either stand-alone or in conjunction with chemical approaches, are playing an increasing role in this field. The primary aim of this review is to highlight recent advances in qualitative and quantitative detection of impurities at trace levels, with a particular focus on GTIs.     

Recent advances in analytical methods for the therapeutic drug monitoring of immunosuppressive drugs

Therapeutic drug monitoring (TDM) of immunosuppressive drugs (ISDs) with a narrow therapeutic index is an increasingly popular tool for minimizing drug toxicity while maximizing the prevention of graft loss and organ rejection. This review focuses on trends regarding analytical methods for the TDM of ISDs since 2011. The five most commonly prescribed immunosuppressive medications are critically reviewed: cyclosporine A, tacrolimus, sirolimus (rapamycin), everolimus, and mycophenolic acid. This review introduces the general background of TDM and ISDs and presents the recent developments in using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and immunoassays for the TDM of ISDs. Finally, a future perspective for these analytical methods is briefly discussed.     

Recent advances in protein tyrosine phosphatase detection using chemical probes

Protein tyrosine phosphatases (PTPs) are key regulatory enzymes in signal transduction pathways and their aberrancy has been implicated in various diseases such as cancers, metabolic syndrome, and autoimmune disorders. In spite of its great importance, determination of the functional significance of PTPs remains a major challenge, and efficient methodologies are needed to specifically delineate PTP functions. Besides the strategy to use potent and selective PTP inhibitors to study the physiological roles of the enzymes, measurement of PTP activities using specific PTP substrates or activity-based probes (ABPs) has been reported. This review focused on the recent development of small molecular probes to detect PTP activities, consisting of five sub-categories: 1. Conventional fluorescent substrates; 2. Ratiometric fluorescent PTP substrates; 3. Fluorescence substrates with selectivity to a single PTP or a class of PTPs; 4. ABPs specific for PTPs; and 5. A real-time imaging of PTP-substrate complex using a small molecule PTP probe which, offers a measurement of a real-time activity of a certain PTP in cells.     

Recent advances in protein-protein interaction prediction: experimental and computational methods

Introduction: Proteins within the cell act as part of complex networks, which allow pathways and processes to function. Therefore, understanding how proteins interact is a significant area of current research. Areas covered: This review aims to present an overview of key experimental techniques (yeast two-hybrid, tandem affinity purification and protein microarrays) used to discover protein-protein interactions (PPIs), as well as to briefly discuss certain computational methods for predicting protein interactions based on gene localization, phylogenetic information, 3D structural modeling or primary protein sequence data. Due to the large-scale applicability of primary sequence-based methods, the authors have chosen to focus on this strategy for our review. There is an emphasis on a recent algorithm called Protein Interaction Prediction Engine (PIPE) that can predict global PPIs. The readers will discover recent advances both in the practical determination of protein interaction and the strategies that are available to attempt to anticipate interactions without the time and costs of experimental work. Expert opinion: Global PPI maps can help understand the biology of complex diseases and facilitate the identification of novel drug target sites. This study describes different techniques used for PPI prediction that we believe will significantly impact the development of the field in a new future. We expect to see a growing number of similar techniques capable of large-scale PPI predictions.     

Recent advances in the pharmacological management of infections due to multidrug-resistant Gram-negative bacteria

ABSTRACT

Introduction: The emergence and diffusion of multidrug-resistant Gram-negative bacteria (MDR-GNB) is an unprecedented threat, with prevalences as high as 10–50% being reported in many countries.

Areas covered: In the present review, we discuss the management of infections due to MDR-GNB, focusing in particular on current strategies and novel agents with already available results from phase 3 randomized controlled trials.

Expert commentary: Some new drugs, such as ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam, which have become available in the past months, have increased our chance of improving survival in severe carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae infections; while others, with potent activity against carbapenem-resistant Acinetobacter baumannii which is currently the highest priority regarding the need for novel agents, will become available in the near future. In the meantime, the focus of both clinical practice and research is slowly but steadily widening from efficacy and tolerability of new treatment options to also future preservation of their antimicrobial activity. This is reflected in clinical practice by more attention paid to antimicrobial stewardship initiatives, and in clinical research by growing interest in exploring resistance development as a major endpoint in both preclinical and clinical studies.     

Recent advances in predicting lncRNA–disease associations based on computational methods

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Recent advances in nephrology

The 31st Annual Meeting of the American Society of Nephrology, held in Philadelphia, Pennsylvania, USA, October 25-28, 1998, presented the newest advances in basic and clinical nephrology science. Several presentations discussed the results of studies with the newer immunosuppressants such as tacrolimus, sirolimus, mycophenolate mofetil and the anti-CD25 monoclonal antibodies, with the conclusion that studies on long-term use of these agents are needed. A number of other issues on immunosuppression protocols in renal transplantation were addressed during the meeting, including the subjects of steroid withdrawal and the role of TGF-beta in the development of chronic allograft nephropathy. The use of NESP in the treatment of renal anemia, the use of sildenafil to treat erectile dysfunction in hemodialysis patients, and the use of ACE inhibitors in nondiabetic renal patients were other important issues discussed at this meeting. Newer approaches to the treatment of hypertension discussed at the meeting highlighted the potential role of angiotensin II receptor antagonists in renal disease patients. Researchers also presented the promising results of a trial of a new, hybrid cell vaccine approach to the treatment of renal cell carcinoma.     

抗抑郁药临床应用的进展

抗抑郁药是治疗抑郁症和抑郁症状的主要药物,近10余年来,从药物作用机制到药物的疗效和安全性得到了飞快地发展。使得治疗抑郁症和抑郁症状的药物具有更多的选择,为临床提高疗效、减少药物不良反应和减少疾病复发提供更多的手段。     

Recent advances in kartogenin for cartilage regeneration

Either osteoarthritis or sports-related injuries can lead to cartilage defects, whereas both chondrocyte self-renewal and conventional treatments face limitations. In cartilage regenerative medicine, growth factors are commonly used to induce chondrogenic differentiation of stem cells. However, application of growth factors is confined by some drawbacks. Emerging small molecules are regarded as an alternative for cartilage regeneration. A recently discovered small-molecule compound, kartogenin (KGN), has been proven to be a chondrogenic and chondroprotective agent and is more effective in inducing cartilage regeneration when compared with growth factors. KGN has been processed and applied in many forms, such as in intra-articular injection, in collaboration with growth factors, in incorporation in drug delivery systems, and in combination with scaffolds. Fortunately, progress has been achieved in KGN applications. The current review discusses the recent advances in KGN for cartilage regeneration and thus presents new concepts in cartilage repair in clinical settings.