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Background: Chronic lung diseases are the third leading cause of death in the United States due in part to an incomplete understanding of pathways that govern the progressive tissue remodeling that occurs in these disorders. Adenosine is elevated in the lungs of animal models and humans with chronic lung disease where it promotes air-space destruction and fibrosis. Adenosine signaling increases the production of the pro-fibrotic cytokine interleukin-6 (IL-6). Based on these observations, we hypothesized that IL-6 signaling contributes to tissue destruction and remodeling in a model of chronic lung disease where adenosine levels are elevated. Methodology/Principal Findings: We tested this hypothesis by neutralizing or genetically removing IL-6 in adenosine deaminase (ADA)-deficient mice that develop adenosine dependent pulmonary inflammation and remodeling. Results demonstrated that both pharmacologic blockade and genetic removal of IL-6 attenuated pulmonary inflammation, remodeling and fibrosis in this model. The pursuit of mechanisms involved revealed adenosine and IL-6 dependent activation of STAT-3 in airway epithelial cells. Conclusions/Significance: These findings demonstrate that adenosine enhances IL-6 signaling pathways to promote aspects of chronic lung disease. This suggests that blocking IL-6 signaling during chronic stages of disease may provide benefit in halting remodeling processes such as fibrosis and air-space destruction. [ABSTRACT FROM AUTHOR]

Abstract: The main conclusion is that systems biology approaches can indeed advance cancer research, having already proved successful in a very wide variety of cancer-related areas, and are likely to prove superior to many current research strategies. Major points include: [•] Systems biology and computational approaches can make important contributions to research and development in key clinical aspects of cancer and of cancer treatment, and should be developed for understanding and application to diagnosis, biomarkers, cancer progression, drug development and treatment strategies. [•] Development of new measurement technologies is central to successful systems approaches, and should be strongly encouraged. The systems view of disease combined with these new technologies and novel computational tools will over the next 5–20years lead to medicine that is predictive, personalized, preventive and participatory (P4 medicine). [•] Major initiatives are in progress to gather extremely wide ranges of data for both somatic and germ-line genetic variations, as well as gene, transcript, protein and metabolite expression profiles that are cancer-relevant. Electronic databases and repositories play a central role to store and analyze these data. These resources need to be developed and sustained. [•] Understanding cellular pathways is crucial in cancer research, and these pathways need to be considered in the context of the progression of cancer at various stages. At all stages of cancer progression, major areas require modelling via systems and developmental biology methods including immune system reactions, angiogenesis and tumour progression. [•] A number of mathematical models of an analytical or computational nature have been developed that can give detailed insights into the dynamics of cancer-relevant systems. These models should be further integrated across multiple levels of biological organization in conjunction with analysis of laboratory and clinical data. [•] Biomarkers represent major tools in determining the presence of cancer, its progression and the responses to treatments. There is a need for sets of high-quality annotated clinical samples, enabling comparisons across different diseases and the quantitative simulation of major pathways leading to biomarker development and analysis of drug effects. [•] Education is recognized as a key component in the success of any systems biology programme, especially for applications to cancer research. It is recognized that a balance needs to be found between the need to be interdisciplinary and the necessity of having extensive specialist knowledge in particular areas. [•] A proposal from this workshop is to explore one or more types of cancer over the full scale of their progression, for example glioblastoma or colon cancer. Such an exemplar project would require all the experimental and computational tools available for the generation and analysis of quantitative data over the entire hierarchy of biological information. These tools and approaches could be mobilized to understand, detect and treat cancerous processes and establish methods applicable across a wide range of cancers. [Copyright &y& Elsevier]

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRNA biomarkers that can be used to assess response to glucose lowering treatments would be useful. Using patient plasma samples from a subset of the Danish Metagenomics of the Human Intestinal Tract (MetaHIT) cohort, we characterized miRNAs from whole plasma, plasma-derived EVs, and EV-depleted plasma by small RNA-sequencing to identify T2DM associated miRNAs. We identified several miRNAs that exhibited concentration changes between controls and non-metformin treated T2DM patients and we validated a subset of these by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results showed that the concentrations of many T2DM-affected miRNAs in EV (but not in whole or EV-depleted plasma) decreased to levels close to those of healthy controls following metformin treatment. Among other potential uses of these differentially expressed miRNAs, some might be useful in assessing the response to metformin in T2DM patients. [ABSTRACT FROM AUTHOR]

The U.S. societal enterprise that people call science is superb. Its remarkable power and reach as part of the international scientific community today are unique in history. But people must remember that American scientific expertise in virtually every field has been leveraged by the rise over the past 40 years of this global scientific community. English is the language of science today not because of the English industrial revolution or even because of giants like Newton, Faraday, Maxwell, and Darwin, but because of what has happened to science since World War II. The reality of this phenomenon is particularly evident in the biological sciences. The knowledge explosion in biology over the past few decades has been dramatic and thoroughly international. The United States has benefited remarkably from tapping into a wide range of global talent, energy, and scientific creativity. In a world where security and unity are threatened daily, the global reality of a worldwide scientific enterprise represents both a real value and a symbol of the security of humanity. However, the international character of the scientific enterprise is in danger.