Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine

Modern medical practice relies heavily on the use of highly purified pharmaceutical compounds whose purity can be easily assessed and whose pharmaceutical activity and toxicity show clear structure-function relationships. In contrast, many herbal medicines contain mixtures of natural compounds that have not undergone detailed chemical analyses and whose mechanism of action is not known. Traditional folk medicine and ethno-pharmacology coupled to bioprospecting have been an important source of many anticancer agents as well as other medicines. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicine. As the example of medicinal mushrooms demonstrates, however, translating traditional Eastern practices into acceptable evidence-based Western therapies is difficult. Different manufacturing standards, criteria of purity, and under-powered clinical trials make assessment of efficacy and toxicity by Western standards of clinical evidence difficult. Purified bioactive compounds derived from medicinal mushrooms are a potentially important new source of anticancer agents; their assimilation into Western drug discovery programs and clinical trials also provides a framework for the study and use of other traditional medicines.     

Integrating noninvasive molecular imaging into molecular medicine: an evolving paradigm

Molecular imaging is a rapidly emerging field, providing noninvasive visual quantitative representations of fundamental biological processes in intact living subjects. Fundamental biomedical research stands to benefit considerably from advances in molecular imaging, with improved molecular target selection, probe development and imaging instrumentation. The noninvasiveness of molecular imaging technologies will also provide benefit through improved patient care. Molecular imaging endpoints can be quantified, and therefore are particularly useful for translational research. Integration of the two disciplines of molecular imaging and molecular medicine, combined with systems-biology approaches to understanding disease complexity, promises to provide predictive, preventative and personalized medicine that will transform healthcare.     

Parahippocampal cortex: translating vision into space

Two recent imaging studies have shed new light on information representation in human parahippocampal cortex. Despite their different approaches, the two studies both support the view that this brain region represents space at an elementary level.     

Effect of the molecular structure of anthracycline compounds on their intercalation into DNA

Kinetics of interaction of rubomycin, carminomycin, and their C9-analogues with deoxyribonucleic acid have been studied by the stop - flow method. Possible reasons of nonexponentiality of the kinetic curves are discussed. The rate constants of direct and reverse intercalation of the drugs between DNA base pairs were determined and relatively small differences found for various drugs. These data and of equilibrium binding studies of interaction of the antibiotics and their analogs with DNA led to conclusion that C9-modification of anthracyclines has little effect on the binding process. That was confirmed by quantum-mechanic calculations of potential energy of interaction between various anthracycline aglicones and DNA base-pairs.     

Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine

Realizing personalized medicine requires integrating diverse data types with bioinformatics. The most vital data are genomic information for individuals that are from advanced next-generation sequencing (NGS) technologies at present. The technologies continue to advance in terms of both decreasing cost and sequencing speed with concomitant increase in the amount and complexity of the data. The prodigious data together with the requisite computational pipelines for data analysis and interpretation are stressors to IT infrastructure and the scientists conducting the work alike. Bioinformatics is increasingly becoming the rate-limiting step with numerous challenges to be overcome for translating NGS data for personalized medicine. We review some key bioinformatics tasks, issues, and challenges in contexts of IT requirements, data quality, analysis tools and pipelines, and validation of biomarkers.     

Alcoholic liver disease: new insights into mechanisms and preventative strategies

Alcoholic liver disease has a known aetiology but a complex pathogenesis. It is an extremely common disease with a high mortality, but the reason why only a relatively small proportion of heavy drinkers progress to advanced disease remains elusive. Accumulating evidence points towards an elaborate interplay between metabolism, inflammation and immunity in the development of steatosis, hepatitis and fibrosis. These complex pathways leading to liver injury offer many potential susceptibility loci, as well as sites for potential therapeutic intervention.     

From lab to lifestyle: translating genomics into healthcare practices

Contemporary genomic sciences are uncovering genetic factors implicated in common complex diseases such as type 2 diabetes. It is suggested that such knowledge could be developed into tests for susceptibility to the disease that would allow preventive action through lifestyle modification. This paper presents research on responses to this suggestion by genetic specialists, diabetologists, and general practitioners – three groups of health professionals whose practices are likely to be affected by such testing services. It shows how the responses of the different groups are related to the professional culture of practice. I suggest that the perspective a profession has of its potential role in relation to the emerging technology can illuminate the early stages of co-constitution by which the technology that is used and the community of practice that use it are mutually reshaped.     

Risk factors for autism: translating genomic discoveries into diagnostics

Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a ‘standard of care’ test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.     

Adult attention deficit hyperactivity disorder: translating research into practice

Attention deficit hyperactivity disorder (ADHD) in adults is a prevalent, yet under-appreciated, under-researched and poorly understood condition. Given this, it is imperative that information and awareness regarding this condition are made more widespread, both amongst the general public and amongst healthcare professionals. Further, given our poor understanding of the aetiology of the condition, meaningful translational research that migrates into and better informs clinical practice must be a priority. In this brief review we highlight areas regarding the clinical diagnosis and management of ADHD in adults (guidelines, rating scales, pharmacotherapy, psychotherapy) as well as areas of promising translational research (genetics, neuroimaging, sleep and circadian rhythms, animal models of ADHD). We address some of the challenges presented for both clinicians and healthcare providers and research scientists working to improve the lives of those adults with ADHD.     

The proposed benefits of incorporating non-human animals into preventative efforts for Conduct Disorder

Abstract

Conduct disorder (CD) is among the most intractable mental health problems and has been found to be increasingly prevalent throughout childhood, and into adolescence. Although many of the behaviors that comprise CD have been researched, there has been limited focus on preventative interventions for childhood conduct problems. This article reviews risk factors for the development of CD, which include the characteristics of early-starting conduct-disordered children, their parents and families. I then discuss directions for future preventative efforts with particular focus on the promotion of concern for others, and the development of positive interpersonal relationships. To this end, I provide a detailed rationale for the proposal that animal-assisted preventative efforts are an optimal vehicle for promoting positive functioning, and thereby interrupting the development of CD.     

Estrogen receptor-beta and breast cancer: translating biology into clinical practice

Estrogen receptor (ER) β was discovered over a decade ago. The design of most studies on this receptor was based on knowledge of its predecessor, ERα. Although breast cancer (BCa) has been a main focus of ERβ research, its precise roles in breast carcinogenesis remain elusive. Data from in vitro models have not always matched those from observational or clinical studies. Several inherent factors may contribute to these discrepancies: (a) several ERβ spliced variants are expressed at the protein level, and isoform-specific antibodies are unavailable for some variants; (b) post-translational modifications of the receptor regulate receptor functions; (c) the role of the receptor differs significantly depending on the type of ligands, cis-elements, and co-regulators that interact with the receptor; and (d) the diversity of distribution of the receptor among intracellular organelles of BCa cells. This review addresses the gaps in knowledge in ERβ research as it pertains to BCa regarding the following questions: (1) is ERβ a tumor suppressor in BCa?; (2) do ERβ isoforms play differential roles in breast carcinogenesis?; (3) do nuclear signaling and extranuclear ERβ signaling differ in BCa?; (4) what are the consequences of post-translational modifications of ERβ in BCa?; (5) how do co-regulators and interacting proteins increase functional diversity of ERβ?; and (6) how do the types of ligand and regulatory cis-elements affect the action of ERβ in BCa?. Insights gained from these key questions in ERβ research should help in prevention, diagnosis/prognosis, and treatment of BCa.