MicroRNAs (miRNAs) are short 18–23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3′ untranslated region (3′ UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3′ UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype.
Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a potentially life-threatening infection that can affect humans and a wide variety of animals in the tropics. In December 2017, a swine melioidosis case was discovered during a meat inspection at a privately-owned slaughterhouse in Nakhon Si Thammarat Province in southern Thailand. The infection, which continued for several months, caused a dispute about where the disease began. An environmental investigation into two farms—both involved in raising the first infected pig—ensued. Through genetic analysis, the investigation revealed that a contaminated water supply at one farm was the probable source of infection. The three local sequence types identified in the investigation were types 51, 298 and 392.
Obesity and overweight are strongly associated with dyslipidemia which can promote the development of cardiovascular diseases. Recently, natural products have been suggested as alternative compounds for antioxidant and antilipidemic activity. The objective of this study was to determine the phenolic compounds and assess the inhibitory activities on pancreatic lipase, cholesterol esterase, and cholesterol micellization of nipa palm vinegar (NPV). Total phenolic content was assessed and phenolic compounds were determined using the Folin–Ciocalteu assay and liquid chromatography-mass spectrometry (LC-MS), respectively. Pancreatic lipase and cholesterol esterase inhibitory activities of the NPV were measured using enzymatic colorimetric assays. The formation of cholesterol micelles was assessed using a cholesterol assay kit. The phenolic content of NPV was 167.10 ± 10.15 µg GAE/mL, and LC-MS analyses indicated the presence of gallic acid, isoquercetin, quercetin, catechin, and rutin as bioactive compounds. Additionally, the NPV inhibited pancreatic lipase and cholesterol esterase activities in a concentration-dependent manner. Moreover, the NPV also suppressed the formation of cholesterol micellization. These results suggest that phenolic compounds, especially gallic acid, isoquercetin, quercetin, catechin, and rutin, from NPV may be the main active compounds with possible cholesterol-lowering effects through inhibition of pancreatic lipase and cholesterol esterase activities as well as the inhibition of solubility of cholesterol micelles. Therefore, NPV may delay postprandial dyslipidemia, and it could be used as a natural source of bioactive compounds with antilipidemic activity. However, NPV should be extensively evaluated by animal and clinical human studies.
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