Farah Dall (curlerspear10)

In both genders, hierarchical clustering of RNA-seq data demonstrates several gene ontologies responded differently in CDAHFD-fed Cyp2b-null mice compared to WT mice (lipid metabolism > fibrosis > inflammation). Oil Red O staining and direct triglycerides measurements confirmed that CDAHFD-fed Cyp2b-null females were protected from NAFLD. CDAHFD-fed Cyp2b-null mice showed equivocal changes in fibrosis with transcriptomic and serum markers suggesting less inflammation due to glucocorticoid-mediated repression of immune responses. In contrast to females, CDAHFD-fed Cyp2b-null males had higher triglyceride levels. Results indicate that female Cyp2b-null mice are protected from NAFLD while male Cyp2b-null mice are more susceptible to NAFLD, with few significant changes in NASH development. This study confirms that increased NAFLD development does not necessarily lead to progressive NASH. Furthermore, it indicates a role for Cyp2b in fatty liver disease that differs based on gender.BACKGROUND & AIM Accumulated evidence indicates that the elevation of lipid metabolism is an essential step in colorectal cancer (CRC) development, and analysis of the key lipogenic mediators may lead to identifying the new clinically useful prognostic gene signatures. METHODS The expression pattern of 61 lipogenic genes was assessed between CRC tumors and matched adjacent normal tissues in a training set (n = 257) with the Mann-Whitney U test. Cox's proportional hazards model and the Kaplan-Meier method were used to identifying a lipogenic-biomarkers signature associated with the prognosis of CRC. The biomarkers signature was then confirmed in two independent validation groups, including a set of 223 CRC samples and an additional set of 203 COAD profiles retrieving from the Cancer Genome Atlas (TCGA). RESULTS Five genes, including ACOT8, ACSL5, FASN, HMGCS2, and SCD1, were significantly enhanced in CRC tumors. Using the cutoff value 0.493, the samples were classified into high risk and low risk. The AUC of panel for discriminating of all, early (I-II stages), and advanced CRC (III-IV stages) were 0.8922, 0.8446, and 0.9162 (Training set), along with 0.8800, 0.8205, and 0.7351 (validation set I), and 0.9071, 0.8946, and 0.9107 (Validation set II), respectively. There was a reverse correlation between the high predicted point of panel and worse OS of CRC patients in training set (HR (95% CI) 0.1096 (0.07089-0.1694), P less then 0.001), validation set I (HR (95% CI) 0.3350 (0.2116-0.5304), P less then 0.001), and validation set II (HR (95% CI) 0.1568 (0.1090-0.2257), P less then 0.001). CONCLUSION Our study showed that the panel of ACOT8/ACSL5/FASN/HMGBCS2/SCD1 genes had a better prognostic performance than validated clinical risk scales and is applicable for early detection of CRC and tumor recurrence.INTRODUCTION Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults. METHODS Healthy participants aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed. RESULTS Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimen