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  • 1
    Publication Date: 2018-08-21
    Description: A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite–induced epithelial cell cytokine production and reduced CD4 + T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level–dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2018-06-02
    Description: Objective Although the role of microRNA-17 (miR-17) has been identified as a tumour biomarker in various studies, its prognostic value in cancers remains unclear. Therefore, we performed a systematic review and meta-analysis to analyse and summarise the relationship between the miR-17 status and clinical outcome in a variety of human cancers. Design Systematic review and meta-analysis. Data sources PubMed, Web of Science and Embase from the first year of records to 15 May 2017. Outcomes The patients’ survival results were pooled, and pooled HRs with 95% CIs were calculated and used for measuring the strength of association between miR-17 and the prognosis of cancers, including hepatocellular carcinoma, lung cancer, osteosarcoma, glioma, T-cell lymphoblastic lymphoma and colon cancer. Heterogeneity, publication bias and subgroup analysis were also conducted. Results A total of 1096 patients were included in this meta-analysis from 12 articles. The results indicated that the increased expression of miR-17 played an unfavourable role in overall survival in various human carcinomas with the HR of 1.342 taking into account the publication bias. In subgroup analysis, HR of ethnicity (Caucasian HR=1.48 and Asian HR=1.40), disease (digestive system HR=1.36 and blood system cancer (HR=2.38), detection method (quantitative real-time PCR HR=1.40 and in situ hybridisation, HR=2.59) and detection sample (tissue HR=1.45 and serum HR=1.32) were significant with p〈0.05. For the analysis of disease-free survival and recurrence-free survival, the increased expression of miR-17 was associated with unfavourable prognosis (HR=1.40). Conclusions miR-17 may be a useful biomarker in predicting the clinical outcome of human cancers, but due to the limitations of the current studies, further verification of the role of miR-17 in human malignancies is urgently needed. PROSPERO registration number CRD42017065749
    Keywords: Open access, Genetics and genomics
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 3
    Publication Date: 2018-03-07
    Description: Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP –/– mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP –/– mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as Mogibacterium neglectum , Desulfovibrio piger , and Desulfomicrobium orale , were increased in feces of CRAMP –/– mice and were transferred to WT mice during cohousing. When littermates of CRAMP +/– parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP –/– and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 4
    Publication Date: 2018-02-16
    Description: Objectives To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. Design This was a multicentre, retrospective, observational study. Setting 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 Participants Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. Primary and secondary outcome measures Resource use for CAP management. Results Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. Conclusions These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. Trial registration number NCT02489578 ; Results.
    Keywords: Open access, Infectious diseases
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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