The benefits of in silico modeling to identify possible small-molecule drugs and their off-target interactions

Accepted for publication in a future issue of Future Medicinal Chemistry.The research into the use of small molecules as drugs continues to be a key driver in the development of molecular databases, computer-aided drug design software and collaborative platforms. The evolution of computational approaches is driven by the essential criteria that a drug molecule has to fulfill, from the affinity to targets to minimal side effects while having adequate absorption, distribution, metabolism, and excretion (ADME) properties. A combination of ligand- and structure-based drug development approaches is already used to obtain consensus predictions of small molecule activities and their off-target interactions. Further integration of these methods into easy-to-use workflows informed by systems biology could realize the full potential of available data in the drug discovery and reduce the attrition of drug candidates.Peer reviewe

Berberine and Coptidis Rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations

Ethnopharmacological relevance: Coptidis Rhizoma (Huanglian) and its major component, berberine, have drawn extensive attention toward their antineoplastic effects in the recent years. The antineoplastic effects are related to the Chinese Medicine (CM) properties of Huangliang in treating diseases by removing damp-heat and purging fire and counteracting toxicity. Aim of the review: To trace the long history of the traditional use of Huanglian from folk medicines, especially from Chinese medicine, to recent pharmacological studies of Huanglian and berberine, with an emphasis on their antineoplastic effects and the promise as novel antineoplastic agents. Methods: A total of seven databases were extensively searched for literature research. The terms and keywords for searching included Huanglian, berberine, Coptis, Coptidis Rhizoma, anticancer, anti-invasion, antimatastasis and mechanism. The papers including ours with studies on anticancer and mechanism, pharmacology and toxicology of Huanglian and/or berberine were focused. Results: In view of traditional use, the anticancer effects of Huanglian can be ascribed to its CM trait by removing damp-heat, fire and toxicity. From modern biomedical studies, anticancer effects have been demonstrated in both Huanglian and berberine. The underlying molecular mechanisms involve cell-cycle arrest, apoptosis induction and anti-inflammation. Berberine is an essential anticancer compound in Huanglian. In some studies, the use of Huanglian was shown to be more effective and beneficial than the use of berberine alone. The presence of other protoberberine-type alkaloids in Huanglian might give synergistic effects for the anticancer effects. Berberine also demonstrates effects of antiangiogenesis, anti-invasion and anti-metastasis in some cancer cell lines, however, more investigations are required to unravel the underlying mechanisms involved. Conclusions: The modern evidences of treating cancer with Huanglian and berberine have a strong linkage with traditional concept and rules of using Huanglian in CM practice. As anticancer candidates with low toxicity, berberine and its altered structure, as well as Huanglian and its formulae, will attract scientists to pursue the potential anticancer effects and the mechanisms by using technologies of genomics, proteomics and other advanced approaches. On the other hand, relatively few in vivo studies have been conducted on anticancer effects of Huanglian and berberine. The clinical application of berberine or Huanglian as novel cancer therapeutic agents requires in vivo validations and further investigations of their anticancer mechanisms. © 2009 Elsevier Ireland Ltd. All rights reserved.published_or_final_versio

Review on Approaches of A Reverse Vaccinology for Dangerous Pathogens of Animal

The traditional method of vaccine development includes pathogen culture in the laboratory, but this is not possible in the case of highly infectious pathogens that are hazardous to culture in the laboratory.Reverse vaccinology is regarded as a low-cost and effective method for screening the entire pathogen genome. The incorporation of the pangenome concept into the reverse vaccinology approach is critical in the search for broad-spectrum immunogenic targets and the analysis of closely related bacterial species.. The heart of reverse vaccinology is the selection of specific epitopes of interest capable of eliciting both cellular and humoral immune responses. Reverse vaccinology has also been used to combat viruses. The processes behind the development of protective immunity, and the principles that will direct the creation of the next generation of vaccines by using genomic techniques to investigate both the pathogen and the host. This review demonstrates the advancement of reverse vaccination, their applicability, and their limitations in the timely creation of effective vaccines against the most deadly infections. Keywords: Vaccines, Epitope Prediction, Immunizations,Reverse Vaccinology DOI: 10.7176/JBAH/13-15-03 Publication date:September 30th 202

The re-emergence of natural products for drug discovery in the genomics era

Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery

Elucidating the Relationship between Chinese Medicine and Systems Biology: A Multi-Sited Ethnography

Ever since Chinese medicine encountered modern science in the late nineteenth century, the relationship between the two traditions has been extremely one-sided. At best, scientists perceived Chinese medicine as an archive of primitive knowledge from which potentially useful drugs could be extracted. Chinese medicine practitioners themselves, meanwhile, began a long struggle throughout the twentieth century to modernise their medicine with the help of Western theories and technology. At the turn of the twenty-first century, the involvement of systems biologists in Chinese medicine research created a new encounter, however, that, at least in the rhetoric of its actors, promised a very different kind of relationship: a match of two systems brought together by a shared interest in understanding life, health, illness and medicine as intrinsically complex and not amenable to the reductionist approaches of mainstream science. This research empirically investigates the nature of this relationship and how it emerged. It aims to contribute to the contemporary history of Chinese medicine by exploring the relationship between Chinese medicine and systems biology. This thesis argues that a heterogeneous network evolved, which is composed of human and nonhuman actors and their interactions created globally distributed research projects on Chinese medicine and systems biology. For the purpose of this research, a multi-sited ethnography was conducted over a period of eleven months and a literature survey was employed to trace the start and the development of this heterogeneous network. Ethnographic data reveals in four chapters on the rhetoric and perceptions of the actors, their involvement in Chinese medicine research, their laboratory practice, and the networks and political ties, which developed into a heterogeneous network of Chinese medicine and systems biology research. This research concludes that in the 2000s, a heterogeneous network emerged through the shared ideologies of systems thinking and holism. The shared ideologies set the groundwork for systems biologists to engage with Chinese medicine on its own terms, and created scientific practices, co-operation and funding opportunities between Europe and China

Rapid prototyping for biomedical engineering: current capabilities and Challenges

A new set of manufacturing technologies has emerged in the past decades to address market requirements in a customized way and to provide support for research tasks that require prototypes. These new techniques and technologies are usually referred to as rapid prototyping and manufacturing technologies, and they allow prototypes to be produced in a wide range of materials with remarkable precision in a couple of hours. Although they have been rapidly incorporated into product development methodologies, they are still under development, and their applications in bioengineering are continuously evolving. Rapid prototyping and manufacturing technologies can be of assistance in every stage of the development process of novel biodevices, to address various problems that can arise in the devices' interactions with biological systems and the fact that the design decisions must be tested carefully. This review focuses on the main fields of application for rapid prototyping in biomedical engineering and health sciences, as well as on the most remarkable challenges and research trends