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Clavulanic acid (CA) is usually used together with other β‐lactam antibiotics as combination drugs to inhibit bacterial β‐lactamases, which is mainly produced from the fermentation of microorganism such as Streptomyces clavuligerus. Recently, it is still a challenge for downstream processing of low concentration and unstable CA from fermentation broth with high solid content, high viscosity, and small cell size. In this study, an integrated process was developed for simultaneous solid–liquid separation and primary purification of CA from real fermentation broth of S. clavuligerus using salting‐out extraction system (SOES). First, different SOESs were investigated, and a suitable SOES composed of ethanol/phosphate was chosen and further optimized using the pretreated fermentation broth. Then, the optimal system composed of 20% ethanol/15% K2HPO4 and 10% KH2PO4 w/w was used to direct separation of CA from untreated fermentation broth. The result showed that the partition coefficient (K) and recovery yield (Y) of CA from untreated fermentation broth were 29.13 and 96.8%, respectively. Simultaneously, the removal rates of the cells and proteins were 99.8% and 63.3%, respectively. Compared with the traditional method of membrane filtration or liquid–liquid extraction system, this developed SOES showed the advantages of simple operation, shorter operation time, lower process cost and higher recovery yield of CA. These results demonstrated that the developed SOES could be used as an attractive alternative for the downstream processing of CA from real fermentation broth. [ABSTRACT FROM AUTHOR]

Aberrant expression of micro RNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. micro RNA-219-5p (miR-219-5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR-219-5p and colorectal cancer ( CRC) metastasis remains unclear. In the present study, miR-219-5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer-binding factor 1 ( LEF1) as a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial-mesenchymal transition ( EMT). Furthermore, silencing LEF1 phenocopied this metastasis-suppressive function. The recovery experiment showed that re-expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR-219-5p. Additionally, we demonstrated that miR-219-5p exerted this tumor-suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR-219-5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR-219-5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis The role of respiratory viral infection in the pathogenesis of chronic rhinosinusitis (CRS) has been rarely studied and remains controversial. The aim of this study was to explore the prevalence of respiratory viruses in the chronic status of CRS. Study Design A case-control prospective study. Methods Fifty-three control subjects, and 67 CRS with nasal polyp (CRSwNP) and 61 CRS without nasal polyp (CRSsNP) patients without signs of acute viral infection were enrolled. Epithelial cells scraped from the middle nasal meatus were tested for the nucleic acid of nine common respiratory viruses using polymerase chain reaction assay. The clinical disease severity was compared between subjects with and without viral infection. Results The overall detection rate of viral infection was 75.47%, 68.66%, and 73.77% in controls, CRSwNP, and CRSsNP, respectively, and no significant difference among studied groups was observed. There was no significant difference in detection rate of any specific individual virus or multiple viruses among the groups studied either. Visual analog scale scores of symptoms, computed tomography scores, or endoscope scores did not show obvious difference between subjects with and without viral infection. Conclusions Although a high frequency of viral infection could be observed in the middle nasal meatus, no increase of frequency of viral infection could be demonstrated in chronic persistent phase of CRSsNP and CRSwNP. The contribution of the interaction between viral infection and host immunity to the pathogenesis of CRS remains to be determined. Level of Evidence 3b. Laryngoscope, 124:832-837, 2014 [ABSTRACT FROM AUTHOR]