Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810]

BACKGROUND: Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. METHODS: Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. RESULTS: Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. CONCLUSIONS: Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent

Genetic polymorphisms associated with the inflammatory response in bacterial meningitis

BACKGROUND Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches

Genomic features and computational identification of human microRNAs under long-range developmental regulation

<p>Abstract</p> <p>Background</p> <p>Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes. Given this functional similarity as well as recent zebrafish transgenesis assays showing that the miR-9 family is indeed regulated by HCNEs with enhancer activity, we hypothesized that this type of miRNA regulation is prevalent. In this paper, we therefore systematically investigate the regulatory landscape around conserved self-transcribed miRNAs (ST miRNAs), with their own known or computationally inferred promoters, by analyzing the hallmarks of GRB target genes. These include not only the density of HCNEs in their vicinity but also the presence of large CpG islands (CGIs) and distinct patterns of histone modification marks associated with developmental genes.</p> <p>Results</p> <p>Our results show that a subset of the conserved ST miRNAs we studied shares properties similar to those of protein-coding GRB target genes: they are located in regions of significantly higher HCNE/enhancer binding density and are more likely to be associated with CGIs. Furthermore, their putative promoters have both activating as well as silencing histone modification marks during development and differentiation. Based on these results we used both an elevated HCNE density in the genomic vicinity as well as the presence of a bivalent promoter to identify 29 putative GRB target miRNAs/miRNA clusters, over two-thirds of which are known to play a role during development and differentiation. Furthermore these predictions include miRNAs of the miR-9 family, which are the only experimentally verified GRB target miRNAs.</p> <p>Conclusions</p> <p>A subset of the conserved miRNA loci we investigated exhibits typical characteristics of GRB target genes, which may partially explain their complex expression profiles during development.</p

Phenotype-independent DNA methylation changes in prostate cancer

BACKGROUND: Human prostate cancers display numerous DNA methylation changes compared to normal tissue samples. However, definitive identification of features related to the cells' malignant status has been compromised by the predominance of cells with luminal features in prostate cancers. METHODS: We generated genome-wide DNA methylation profiles of cell subpopulations with basal or luminal features isolated from matched prostate cancer and normal tissue samples. RESULTS: Many frequent DNA methylation changes previously attributed to prostate cancers are here identified as differences between luminal and basal cells in both normal and cancer samples. We also identified changes unique to each of the two cancer subpopulations. Those specific to cancer luminal cells were associated with regulation of metabolic processes, cell proliferation and epithelial development. Within the prostate cancer TCGA dataset, these changes were able to distinguish not only cancers from normal samples, but also organ-confined cancers from those with extraprostatic extensions. Using changes present in both basal and luminal cancer cells, we derived a new 17-CpG prostate cancer signature with high predictive power in the TCGA dataset. CONCLUSIONS: This study demonstrates the importance of comparing phenotypically matched prostate cell populations from normal and cancer tissues to unmask biologically and clinically relevant DNA methylation changes

Functional annotation of the cattle genome through systematic discovery and characterization of chromatin states and butyrate-induced variations

The functional annotation of genomes, including chromatin accessibility and modifications, is important for understanding and effectively utilizing the increased amount of genome sequences reported. However, while such annotation has been well explored in a diverse set of tissues and cell types in human and model organisms, relatively little data are available for livestock genomes, hindering our understanding of complex trait variation, domestication, and adaptive evolution. Here, we present the first complete global landscape of regulatory elements in cattle and explore the dynamics of chromatin states in rumen epithelial cells induced by the rumen developmental regulator—butyrate.https://doi.org/10.1186/s12915-019-0687-

GRASAS Y ACEITES

Numerous physiological effects are attributed to conjugated linoleic acids (CLA). Biologically active isomers of CLA (cis-9, trans-11 (C 1 8 : 2) and trans-10, cis-1 2 (C 1 8 : 2)) have been reported to have anticarcinogenic, antioxidative and antiatherosclerotic properties. Relatively rich sources of CLA include milk fat-containing foods such as kaymak. Kaymak is a kind of concentrated cream which is traditionally manufactured from buffalo or cow's milk mainly in Turkey,. The objective of this study was to determine CLA concentrations during kaymak production. Kaymak was manufactured from cow's milk which was enriched with unfermented cream. Biologically active isomers of CLA in raw milk, cream and kaymak were analyzed using gas chromatography. The method was quick, repeatable and sensitive for the CLA determination of samples. Significant differences were found among the concentrations of both isomer and total CLA during the production process (p < 0.01). The total GLA contents of raw milk, cream and kaymak were determined as 0.08 +/- 0.02, 0.234 +/- 0.04 and 0.091 +/- 0.08 g/ 100 g lipid, respectively

INTERNATIONAL JOURNAL OF FOOD PROPERTIES

In this research, conjugated linoleic acid (CLA) as the total of cis-9, trans-11, and trans-10, cis-12 isomers of conjugated linoleic acid and -tocopherol contents of traditional Turkish dessert oHosmerimo were determined by Gas-liquid chromatography (GC) with a flame ionization detector (FID) and reversed phase high performance liquid chromatography (RP-HPLC) with UV detection respectively, during 7 days of storage. Processing of lor cheese into hosmerim resulted in 1.5-fold increase in CLA concentration. The contents of CLA and -tocopherol were found as 7.13 +/- 0.06 mg/g lipid and 0.73 +/- 0.03 mg/100 g, respectively, after manufacturing of the product. Hosmerim was evaulated as a good source of CLA and -tocopherol though both nutraceutical compound decreased during 7 days of storage (p 0.01)

MILCHWISSENSCHAFT-MILK SCIENCE INTERNATIONAL

Simultaneous determination of alpha-tocopherol, gamma-tocopherol and delta-tocopherol by reversed-phase liquid chromatography (RP-HPLC) with UV detection in various infant milk formulas sold in Turkey was performed. Analytical method parameters confirmed the quality of the method. Tocopherol isomers in 15 infant formulas ranged from 8.73+/-0.09 to 27.02+/-0.06 mg alpha-tocopherol in 100 g(-1), from 1.67+/-0.04 to 7.28+/-0.10 mg gamma-tocopherol in 100 g(-1); from 0.87+/-0.05 to 1.81+/-0.03 mg delta-tocopherol in 100 g(-1)