The antitumor activities of deguelin appear to involve its binding to the ATP-binding pocket of Hsp90, which suppresses Hsp90 function.

Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of deguelin on Akt activation and lung tumorigenesis in transgenic mice in which Akt expression was induced by tamoxifen and in 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)/benzo(a)pyrene (BaP)-treated A/J mice. Deguelin suppressed Akt activation in vivo, as measured by immunohistochemistry and immunoblotting, and statistically significantly reduced NNK/BaP-induced lung tumor multiplicity, volume, and load in A/J mice, as monitored by microcomputed tomography image analysis, with no detectable toxicity. These results indicate that deguelin warrants consideration as a chemopreventive agent for early-stage lung carcinogenesis in a clinical lung cancer chemoprevention trial.

Single-cell transcriptomic profiles analysis has proposed new insights for understanding the behavior of human gastric cancer (GC). GC offers a unique model of intratumoral heterogeneity. However, the specific classes of cells involved in carcinogenetic passage, and the tumor microenvironment of stromal cells was poorly understood. We characterized the heterogeneous cell population of precancerous lesions and gastric cancer at the single-cell resolution by RNA sequencing. We identified 10 gastric cell subtypes and showed the intestinal and diffuse-type cancer were characterized by different cell population. We found that the intestinal and diffuse-type cancer cells have the differential metaplastic cell lineages: intestinal-type cancer cells differentiated along the intestinal metaplasia lineage while diffuse-type cancer cells resemble de novo pathway. We observed an enriched CCND1 mutation in premalignant disease state and discovered cancer-associated fibroblast cells harboring pro-stemness properties. In particular, tumor cells could be categorized into previously proposed molecular subtypes and harbored specific subtype of malignant cell with high expression level of epithelial-myofibroblast transition which was correlated with poor clinical prognosis. In addition to intratumoral heterogeneity, the analysis revealed different cellular lineages were responsible for potential carcinogenetic pathways. Single-cell transcriptomes analysis of gastric pre-cancerous lesions and cancer may provide insights for understanding GC cell behavior, suggesting potential targets for the diagnosis and treatment of GC.

and curriculum development, and a specialist in first aid evidence evaluation methodology and guideline development.The task force convened in June 2013 to review the topics and questions that were evaluated in 2005 and 2010, past research questions formulated in the PICO style (population, intervention, comparator, outcomes) that were never completed, and the new questions that had been submitted since 2010 to the task force, and a priority list created. Topics were reviewed for areas of controversy, known additional new science, and subject matter not previously evaluated. Task force members created a priority list for review, and the top 10 priority-ranked PICO questions were assigned. After the successful commencement of the workflow, the task force co-chairs added a further 12 PICO questions, including 5 new questions, 1 derived question, and 6 that had been previously reviewed. Selected PICO questions that had been previously reviewed were, in some cases, reworded to facilitate literature searches, and outcomes were decided upon by group consensus.Evidence reviewers were recruited through a call for volunteers distributed by ILCOR to stakeholder organizations around the world. More than 30 individual reviewers were assigned to topics, usually by preference or expertise, but avoiding any direct conflicts of interest. In general, 2 evidence reviewers were assigned to each PICO, supervised by a member of the task force designated as the task force question owner. Evidence reviewers included physicians with diverse specialties including emergency medicine, EMS, wilderness medicine, critical care, cardiology, occupational medicine, toxicology, anesthesia, pediatric emergency medicine, public health, and epidemiology, as well as paramedics, nurse practitioners and first aid education specialists with experience in guideline and curriculum development, and professional evidence evaluation and methodology experts. The Evidence Evaluation ProcessFor the 2015 international evidence evaluation process, the AHA developed a new Web-based information and documentation platform, the Systematic Evidence Evaluation and Review System (SEERS), to support the ILCOR systematic reviews and to capture the data in reusable formats. This Webbased system facilitated structured reviews in a consistent format that would support the ultimate development of science summaries and evidence-based treatment recommendations.Each task force performed a detailed systematic review based on the recommendations of the Institute of Medicine of the National Academies, 1 using the methodological approach proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group.2 After identifying and prioritizing the PICO questions to be addressed, 3 and with the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library).By using detailed inclusion and exclusion criteria, articles were screened for further evalu...

Cronobacter sakazakii is a Gram-negative opportunistic pathogen that causes life- threatening infantile infections, such as meningitis, septicemia, and necrotizing enterocolitis, as well as pneumonia, septicemia, and urinary tract and wound infections in adults. Here, we report 26 draft genome sequences of C. sakazakii, which were obtained from dried spices from the USA, the Middle East, China, and the Republic of Korea. The average genome size of the C. sakazakii genomes was 4393 kb, with an average of 4055 protein coding genes, and an average genome G + C content of 56.9%. The genomes contained genes related to carbohydrate transport and metabolism, amino acid transport and metabolism, and cell wall/membrane biogenesis. In addition, we identified genes encoding proteins involved in osmotic responses such as DnaJ, Aquaproin Z, ProQ, and TreF, as well as virulence-related and heat shock-related proteins.Interestingly, a metabolic island comprised of a variably-sized xylose utilization operon was found within the spice-associated C. sakazakii genomes, which supports the hypothesis that plants may serve as transmission vectors or alternative hosts for Cronobacter species. The presence of the genes identified in this study can support the remarkable phenotypic traits of C. sakazakii such as the organism’s capabilities of adaptation and survival in response to adverse growth environmental conditions (e.g. osmotic and desiccative stresses). Accordingly, the genome analyses provided insights into many aspects of physiology and evolutionary history of this important foodborne pathogen.Electronic supplementary materialThe online version of this article (10.1186/s40793-018-0339-6) contains supplementary material, which is available to authorized users.