Syringin Prevents Aβ25–35-Induced Neurotoxicity in SK-N-SH and SK-N-BE Cells by Modulating miR-124-3p/BID Pathway

Neurochemical Research - Alzheimer’s disease (AD) is a neurodegenerative disorder disease, disturbing people’s normal life. Syringin was mentioned to antagonize Amyloid-β...     

Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene. Here, we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by adipocytes. The edited preadipocytes exhibit a correction of 5.5% of Leptin alleles and produce normal LEPTIN protein when differentiated into mature adipocytes. The ob/ob mice display correction of 1.67% of Leptin alleles, which is sufficient to restore the production and physiological functions of LEPTIN protein, such as suppressing appetite and alleviating insulin resistance. Our study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases, and paves the way for further research on efficient delivery system in potential future clinical application.     

Knockout of Akt1/2 suppresses the metastasis of human prostate cancer cells CWR22rv1 in vitro and in vivo

Although primary androgen deprivation therapy resulted in tumour regression, unfortunately, majority of prostate cancer progress to a lethal castration-resistant prostate cancer, finally die to metastasis. The mutual feedback between AKT and AR pathways plays a vital role in the progression and metastasis of prostate cancer. Therefore, the treatment of a single factor will eventually inevitably lead to failure. Therefore, better understanding of the molecular mechanisms underlying metastasis is critical to the development of new and more effective therapeutic agents. In this study, we created prostate cancer CWR22rv1 cells with the double knockout of Akt1 and Akt2 genes through CRISPR/Cas9 method to investigate the effect of Akt in metastasis of prostate cancer. It was found that knockout of Akt1/2 resulted in markedly reduced metastasis in vitro and in vivo, and appeared to interfere AR nuclear translocation through regulating downstream regulatory factor, FOXO proteins. It suggests that some downstream regulatory factors in the AKT and AR interaction network play a vital role in prostate cancer metastasis and are potential targeting molecules for prostate cancer metastasis treatment.     

Immunohistochemical Expression of RAGE and Its Ligand (S100A9) in Cervical Lesions

Altered expressions of receptor for advanced glycation end-products (RAGE) and its ligand (S100A9) are observed in many cancers and play a key role in inflammation-associated cancer. In our previous study, by two-dimensional gel electrophoresis followed by mass spectrometry, the expression of S100A9 protein was found to increase in squamous cervical cancer compared with adjacent normal cervical tissues. Therefore, in the present study we observed the expressions of S100A9 and RAGE in 30 chronic cervicitis, 50 cervical intraepithelial neoplasia (CIN), and 40 squamous cervical cancer (SCC) using immunohistochemical analysis and analyzed the differential expression and possible role of S100A9 and RAGE in cancer development. Immunohistochemical findings were as follows: the expressions of S100A9 and RAGE were demonstrated in chronic cervicitis, CIN, and SCC. Moreover, their expressions were gradually increasing as the tumor progressed. In SCC, the staining scores of S100A9 and RAGE were significantly higher in well-differentiated tumors compared to moderately and poorly differentiated tumors. The expression of S100A9 in epithelial cells exhibited a positive correlation to RAGE expression in chronic cervicitis, CIN, and SCC. There were no significant difference of S100A9 immunoreactivity in stromal cells among chronic cervicitis, CIN, and SCC. Moreover, there was no correlation between S100A9 immunoreactivity in stromal cells of SCC and clinicopathological parameters. Finally, double immunohistochemistry illustrated that RAGE and S100A9 co-express in SCC. In conclusion, RAGE binds its ligand (S100A9), which plays an important role in the development of SCC. In addition, the expressions of S100A9 and RAGE in SCC tumor cells were closely associated with histological differentiation.     

Isolation and characterization of BTEX tolerant and degrading Pseudomonas putida BCNU 106

Bacterial strains growing in river sediments were screened to identify an organic solvent-tolerant strain of Pseudomonas. Using this screen, Pseudomonas sp. BCNU 106 was isolated on the basis of its ability to grow on benzene, toluene, ethylbenzene, and three xylene isomers, o-, m- and p-xylene, as its sole carbon source. BCNU 106 was identified as a gram-negative, rod-shaped aerobic and mesophilic bacterium, which grew in liquid media containing high concentrations of organic solvents. 16S rDNA analysis classified BCNU 106 as a new member of the genus Pseudomonas. BCNU 106 was distinguishable from other Pseudomonas strains that are tolerant to organic solvents in that the isolate had the ability to utilize all three xylene isomers as well as benzene, toluene and ethylbenzene. The unique properties of the isolate such as solvent-tolerance and the ability to degrade xylene isomers may have important implications for the efficient treatment of solvent wastes.     

Dissolution Properties and Physical Characterization of Telmisartan–Chitosan Solid Dispersions Prepared by Mechanochemical Activation

Solid dispersion systems of telmisartan (a poorly water-soluble antihypertension drug) with biopolymer carrier chitosan have been investigated in this study. The mechanism of solubilization of chitosan for drug has been studied. In addition, the influence of several factors was carefully examined, including the preparation methods, the drug/carrier weight ratios, and the milling time. Drug dissolution and physical characterization of different binary systems were studied by in vitro dissolution test, particle size distribution, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscopy. The results presented that the weak basic property of chitosan appeared as the main driving force for the drug dissolution enhancement. Other effects such as decreased drug crystallinity and size played a positive contributory role. Among the preparation methods, cogrinding was the best method showing strong drug amorphization, reduced particle size, and enhanced dissolution. The drug dissolution markedly improved with increasing the amount of chitosan in solid mixtures. As a result, a significant effect of chitosan increasing telmisartan dissolution has been demonstrated, and cogrinding in a roll ball mill was the best way to prepare solid dispersions, which had high degree of uniformity in drug content and had a practical application in manufacturing.