Antifungal antibiotics

The search for new drugs against fungal infections is a major challenge to current research in mycotic diseases. The present article reviews the current types of antifungal infections, the current scenario of antifungal antibiotics, and the need and approaches to search for newer antifungal antibiotics and antifungal drug targets.     

DNA barcoding,microarrays and next generation sequencing: recent tools for genetic diversity estimation and authentication of medicinal plants

DNA barcoding, microarray technology and next generation sequencing have emerged as promising tools for the elucidation of plant genetic diversity and its conservation. They are proving to be immensely helpful in authenticating the useful medicinal plants for herbal drug preparations. These newer versions of molecular markers utilize short genetic markers in the genome to characterize the organism to a particular species. This has the potential not only to classify the known and yet unknown species but also has a promising future to link the medicinally important plants according to their properties. The newer trends being followed in DNA chips and barcoding pave the way for a future with many different possibilities. Several of these possibilities might be: characterization of unknown species in a considerably less time than usual, identification of newer medicinal properties possessed by the species and also updating the data of the already existing but unnoticed properties. This can assist us to cure many different diseases and will also generate novel opportunities in medicinal drug delivery and targeting.     

Temperature and malaria trends in highland East Africa

There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region. We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglia's Climatic Research Unit database (CRU TS) for several relevant locations. We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996. The trends in the newer data are even more significant when post-1996 data are added to the samples. We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al. We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample. However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level. A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho.     

Optimizing preclinical study design in oncology research

The current drug development pathway in oncology research has led to a large attrition rate for new drugs, in part due to a general lack of appropriate preclinical studies that are capable of accurately predicting efficacy and/or toxicity in the target population. Because of an obvious need for novel therapeutics in many types of cancer, new compounds are being investigated in human Phase I and Phase II clinical trials before a complete understanding of their toxicity and efficacy profiles is obtained. In fact, for newer targeted molecular agents that are often cytostatic in nature, the conventional preclinical evaluation used for traditional cytotoxic chemotherapies utilizing primary tumor shrinkage as an endpoint may not be appropriate. By utilizing an integrated pharmacokinetic/pharmacodynamic approach, along with proper selection of a model system, the drug development process in oncology research may be improved leading to a better understanding of the determinants of efficacy and toxicity, and ultimately fewer drugs that fail once they reach human clinical trials.     

新冠病毒抗体药物研发进展及展望分析

抗体药物以其独特的作用机制和靶向性强、特异性好等优点,在恶性肿瘤、自身免疫性疾病、感染类疾病的诊断和治疗中发挥着越来越重要的作用,成为国际创新药物研发的热点。新冠肺炎(COVID-19)疫情发生以来,国内外多家研究机构和企业正在加快推进新冠病毒(SARS-CoV-2)抗体药物的开发。在此情势下,认真分析抗体药物现状和趋势,梳理国内外新冠病毒抗体药物研究进展,明确我国当前抗体药物创新的机遇、挑战和建议,对加快我国药物自主创新研发具有重要意义。     

生物医药关键技术发展趋势

近年来,生物医药研究人员正在药物的设计、发现、试验、制备,以及检测技术、其他诸如纳米、信息、光学等高技术的融合应用方面致力于更新观念的研究开发,并已取得众多突破,在相关领域形成新的技术趋势。在药物设计方面,随着遗传信息方面的研究进展越来越快,核酸为靶的药物设计已成为新的热点;在疫苗方面,基因疫苗的研制已成为新方向,其技术应用趋向可调控、更安全、更高效生产等,科研人员同时还致力于解决基因疫苗的安全性;在治疗方面,抗体工程和组织工程分别成为药物治疗和组织器官再造的热点;新型药物输送技术正成为业界追逐的目标,药物传输公司正在开发多技术平台,提高药物的效能,减少不良反应和降低成本;药物安全问题已在全球范围内达成共识,美、英、日、欧盟等国均在积极开展药物安全性方面的研究,开发药物安全监测系统;疾病诊断与检测的新技术表现为更高效、准确、快速、早期的趋势,科研人员同时还致力于降低诊断检测产品的价格,以使更多人受益;IT技术、光电技术、纳米技术等新技术正被积极应用于生物医药领域,为大型制药公司和生物技术公司提供药物发现、设计、毒性研究等更新途径的新技术系统。     

The legacy of pharmacogenetics and potential applications

Some 40 years of pharmacogenetic research indicates that knowledge of human genetic diversity is essential to a broader understanding of variation in human drug response, and suggests that drug therapy tailored to the genetic characteristics of the individual may be a realistic goal. Aided by new technologies, molecular studies of genetic polymorphisms of many human enzymes, receptors, and other proteins indicate that only a limited number of important protein variants account for the diversity in drug response, raising the prospect that these variants may be cataloged relatively soon for many human populations. The next great challenge of pharmacogenetics is to pin down the cellular location and effect of these variant proteins on the pathways and networks that govern individual variation in responses to drugs and other exogenous chemicals. In this paper, we will discuss some the current challenges to progress in pharmacogenetics and newer strategies that might be used to improve prospects of drug design and personalized therapy.     

Multi-target drugs: the trend of drug research and development

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.     

核酸自组装纳米递送载体的研究进展

随着核酸纳米技术的飞速发展,核酸自组装纳米载体已成为药物递送领域的研究热点。针对核酸自组装纳米载体在药物递送中的应用进展进行了系统综述,讨论了不同的核酸自组装策略,阐述了多种靶向递送和药物控制释放方法,同时,总结了核酸自组装纳米递送载体在蛋白质药物、核酸药物、小分子药物和纳米药物递送中的应用,并针对该领域的挑战和未来发展趋势进行了总结和展望,以期为药物递送领域和新型药物系统研究提供参考。     

New approaches for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent chronic neurodegenerative disease. Current approved therapies are symptomatic treatments having some effect on cognitive function. Therapies that target β-amyloid (Aβ) have been the focus of efforts to develop a disease modification treatment for AD but these approaches have failed to show any clinical benefit so far. Beyond the ‘Aβ hypothesis’, there are a number of newer approaches to treat AD with neuroinflammation emerging as a very active area of research based on risk gene analysis. This short review will summarize approved drug therapies, recent clinical trials and new approaches for the treatment of AD.     

Chemical probes for tagging mycobacterial lipids

Mycobacteria, which cause tuberculosis and related diseases, possess a diverse set of complex envelope lipids that provide remarkable tolerance to antibiotics and are major virulence factors that drive pathogenesis. Recently, metabolic labeling and bio-orthogonal chemistry have been harnessed to develop chemical probes for tagging specific lipids in live mycobacteria, enabling a range of new basic and translational research avenues. A toolbox of probes has been developed for labeling mycolic acids and their derivatives, including trehalose-, arabinogalactan-, and protein-linked mycolates, as well as newer probes for labeling phthiocerol dimycocerosates (PDIMs) and potentially other envelope lipids. These lipid-centric tools have yielded fresh insights into mycobacterial growth and host interactions, provided new avenues for drug target discovery and characterization, and inspired innovative diagnostic and therapeutic strategies.     

Converging cellular processes for substances of abuse: endogenous morphine

Human and invertebrate tissues have the ability to synthesize morphine, making it an endogenous chemical messenger. Given this new insight we sought to investigate whether substances of abuse have the ability to interact with endogenous morphine processes. Moreover we have shown that cocaine, alcohol and nicotine significantly enhance (125)I-trace labeled morphine release from invertebrate ganglia and human white blood cells. These data and newer research contribute to an evolving hypothesis linking the reinforcing and addictive properties of a variety of drugs of abuse to convergent mechanisms, involving endogenous morphine signaling and establish an opiate foundation as a unifying principle by which we may advance our understanding of polymodal drug abuse mechanisms.     

Antimicrobial Agents with Improved Clinical Efficacy versus Their Persistence in the Environment: Synthetic 4-Quinolone As an Example

There is increasing concern about the effects of pharmaceutical agents in the environment. The use of synthetic 4-quinolone compounds is rapidly increasing: newer and more complex analogues are being developed by the pharmaceutical industry to meet clinical and veterinary needs. This review aims at stimulating the need to consider the fate of pharmaceuticals in the environment as part of overall drug design and development. Currently, regulatory action is triggered if the predicted environmental concentration exceeds an arbitrarily set value, whereas in some countries, there are no regulations at all. By extension, from a clinical perspective, enviropharmacokinetics and enviropharmacodynamics are proposed to quantify the risk to organisms in the environment in a more realistic fashion that is reflective of concentrations at which hazardous effects are observable on such organisms. Such a new approach integrates our knowledge to address ecosystems and related health problems in a more holistic fashion, thus linking public health, environmental degradation, and ecology. Its success requires more collaboration in research and development of newer antibiotics, with their ultimate fate in the environment being central, to bolster the already existing aspirations of controlling the rapid emergence of resistance.     

Conotoxins: From the biodiversity of gastropods to new drugs

The review describes general trends in research of conotoxins, the peptide toxins isolated from sea gastropods of the genus Conus. It covers publications from conotoxin discovery in 1970th up to contemporary research and considers classification of conotoxins, their structural diversity and different ways of their action on molecular targets, particularly, ion channels. Special attention is paid to the applied aspect of conotoxin research especially to perspectives of the development of conotoxin based drugs. The first example of such conotoxin based drug is ziconotide an analgesic of a new generation.     

Seasonal variation of natural products in European trees

The present review gives an overview about the status of research on seasonal variation of natural products in European trees. Due to their different life forms, gymnosperms, deciduous angiosperms, and evergreen angiosperms are reviewed separately. Besides trying to give an overview about the existing newer literature, the review tries to define some repetitively found trends and discusses some possible explanations for these trends. Moreover, open research questions are highlighted and some suggestions for future studies are given. These suggestions encompass both subjects and desirable quality standards with regards to experimental designs. The reviewed publications are mainly focused on leaves, some on fruits, and some on barks and twigs. Phenolics, including phenolic acids and flavonoids of different types as well as tannins, are the most often studied compound class; additionally, some papers assess seasonal variation of alkaloids, diterpenes, essential oils, lignans, simple organic acid, secoiridoids, and stilbenoids.     

Exploiting drug-disease relationships for computational drug repositioning

Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients. As the ability to measure molecules in high-throughput ways has improved over the past decade, it is logical that such data might be useful for enabling drug repositioning through computational methods. Many computational predictions for new indications have been borne out in cellular model systems, though extensive animal model and clinical trial-based validation are still pending. In this review, we show that computational methods for drug repositioning can be classified in two axes: drug based, where discovery initiates from the chemical perspective, or disease based, where discovery initiates from the clinical perspective of disease or its pathology. Newer algorithms for computational drug repositioning will likely span these two axes, will take advantage of newer types of molecular measurements, and will certainly play a role in reducing the global burden of disease.     

Proteomics as a tool for the investigation of seafood and other marine products

The state-of-the-art and future trends of the application of proteomics to seafood and other marine products are reviewed. Consumers' demands for seafood products have increased in the recent years and this situation has underlined the need to guarantee the safety, traceability, authenticity, and health benefits of such products. The increasing presence of commercially available aquaculture products has also prompted the seafood industry to face newer challenges. In this sense, a review of the present status and perspectives of the application of proteomics in the development of newer biotechnology products of marine origin is given.     

Multidrug resistant to extensively drug resistant tuberculosis: What is next?

Drug resistant tuberculosis is a man made problem. While tuberculosis is hundred percent curable, multidrug resistant tuberculosis (MDR-TB) is difficult to treat. Inadequate and incomplete treatment and poor treatment adherence has led to a newer form of drug resistance known as extensively drug resistant tuberculosis (XDR-TB). XDR-TB is defined as tuberculosis caused by Mycobacterium tuberculosis strain, which is resistant to at least rifampicin and isoniazid among the first line anti tubercular drugs (MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second line anti tubercular drugs i.e. amikacin, kanamycin and/or capreomycin. Mismanagement of tuberculosis paves the way to drug resistant tuberculosis. Emergence of XDR-TB is reported world wide. Reported prevalence rates of XDR-TB of total MDR cases are; 6.6% overall worldwide, 6.5% in industrialized countries, 13.6% in Russia and Eastern Europe, 1.5% in Asia, 0.6% in Africa and Middle East and 15.4% in Republic of Korea. Better management and control of tuberculosis specially drug resistant TB by experienced and qualified doctors, access to standard microbiology laboratory, co-morbitidy of HIV and tuberculosis, new anti-TB drug regimens, better diagnostic tests, international standards for second line drugs (SLD)-susceptibility testing, invention of newer antitubercular molecules and vaccines and knowing the real magnitude of XDR-TB are some of the important issues to be addressed for effective prevention and management of XDR-TB.     

Trends in the search for bioactive microbial metabolites

Summary Bioactive microbial metabolites are attracting increasing attention as useful agents for medicine, veterinary medicine, agriculture, and as unique biochemical tools. A review of the current trends in the discovery-of new metabolites shows that the number of active compounds with non-antibiotic type of activity has increased, resulting in an expansion of the variety of bioactivity of microbial metabolites. Factors that contribute to the increased rate of discovery include: development of new methods for activity measurement, exploitation of novel groups of microorganisms as sources of active compounds, new directions for chemical modification, and incorporation of newer knowledge of biotechnology into screening systems. To exemplify this, typical screening methods, and chemical and biological properties of several bioactive compounds obtained by these methods are discussed.     

Eye development at the Houston "Fly Meeting"

The 47th Annual Drosophila Research Conference or "Fly Meeting" took place at Houston, Texas, USA from March 29th- April 2nd, 2006, under the aegis of the Genetics Society of America. The Fly Meeting provides an excellent opportunity for fly researchers to present their work and to get a snapshot of recent developments and upcoming trends in their research field. The fruit fly, Drosophila melanogaster is a very versatile model to study growth, patterning, neural development, evolution, systemetics and various other facets of biomedical science. The topics presented in the meeting covered a very broad spectrum of fly research. In this commentary, I have focused mainly on the presentations related to two fields: 1) research in various fields that use the Drosophila eye as a model system, and 2) the community resources available to all fly researchers.