Probiotics are defined as live, nonpathogenic bacteria that confer health benefits beyond their nutritional value. In particular, VSL#3 exhibits demonstrated efficacy in the management of diseases characterized by an increased intestinal permeability. Our study aimed to understand how VSL#3 promotes gut health by secreting bioactive factors and identify which human pathways are modulated by secretome derived from the VSL#3 formula.
 
  Two different lots of VSL#3 were used, and Caco-2 cell line was treated with conditioned media (CM) prepared using 1 g of the probiotic formula. We evaluated the effects of the probiotics on cellular proliferation and apoptosis by cytometry and the expression of tight junction proteins by western blotting. A proteomics analysis of both culture media and the whole proteome of Caco-2 cells treated with VSL#3-CM was performed by nano-ultra performance liquid chromatography - tandem mass (nUPLC MS/MS) spectrometry.
 
  The probiotic formula increased cell proliferation, decreased cellular apoptosis cells, and increased re-epithelialization in the scratch assay. Several peptides specifically synthetized by all the species within the probiotic preparation were recognized in the proteomics analysis. Human proteins synthesized by CaCo-2 cells were also identified.
 
  To our knowledge, this manuscript describes the first evaluation of the probiotic secretome, and the results showed that the improvement in intestinal barrier functions induced by probiotics seems to be accompanied by the modulation of some human cellular pathways.
 To our knowledge, this manuscript describes the first evaluation of the probiotic secretome, and the results showed that the improvement in intestinal barrier functions induced by probiotics seems to be accompanied by the modulation of some human cellular pathways.
  Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are globally increasing chronic gastro-intestinal inflammatory disorders associating with altered gut microbiota. Infliximab (IFX), a TNF-alpha blocker, is used to treat IBD patients successfully though one third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response.
 
  Our aim was to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients.
 
  72 IBD patients (25 CD and 47 UC) started IFX therapy and were followed for one year or until IFX treatment was discontinued. Amplicon sequencing approach targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately was used to determine the microbiota profiles in faecal samples collected before IFX therapy, two, six, twelve weeks and one year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at twelve weeks after initiation.
 
  Both the faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared to responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients (area under curve > 0.8).
 
  Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.
 Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.Human DNA methylation data have been used to develop biomarkers of ageing, referred to as 'epigenetic clocks', which have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes.  https://www.selleckchem.com/products/toyocamycin.html  Existing DNA methylation clocks have been shown to be highly accurate in blood but are less precise when used in older samples or in tissue types not included in training the model, including brain. We aimed to develop a novel epigenetic clock that performs optimally in human cortex tissue and has the potential to identify phenotypes associated with biological ageing in the brain. We generated an extensive dataset of human cortex DNA methylation data spanning the life course (n = 1397, ages = 1 to 108 years). This dataset was split into 'training' and 'testing' samples (training n = 1047; testing n = 350). DNA methylation age estimators were derived using a transformed version of chronological age on DNA methylation ateed to be considered when building and applying epigenetic clock algorithms to human epidemiological or disease cohorts.Accumulating evidence suggests that chemokines may play an important role in the formation and mediating of the immune microenvironment of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to explore the differences in blood or tissues chemokines concentrations between HCC patients and controls. Online databases, namely PubMed, Web of Science, Embase and Cochrane Library, were systematically searched for relevant articles published on or before 15 January 2020. Standardized mean differences (SMDs) with corresponding 95% confidence intervals of the chemokines concentrations were calculated as group differences between the HCC patients and the controls. Sixty-five studies met the inclusion criteria for the meta-analysis. Altogether they consisted of 26 different chemokines compared between 5828 HCC patients and 4909 controls; and 12 different chemokines receptors compared between 2053 patients and 2285 controls. The results of meta-analysis indicated that concentrations of CCL20, CXCL8 and CXCR4 in the HCC patients were significantly higher than those in the controls (SMD of 6.18, 1.81 and 1.04, respectively). Therefore, higher concentration levels of CCL20, CXCL8 and CXCR4 may indicate the occurrence of HCC Future research should explore the putative mechanisms underlying this linkage. Meanwhile, attempts can be made to replicate the existing findings in prospective cohort populations and explore the cause-and-effect relationships pertaining to this linkage in order to develop new diagnostic and therapeutic strategies for HCC.