Inhibiting NF-κB inducing kinase improved the motor performance of ALS animal model.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear. METHODS: We tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK+/- mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model. RESULTS: In this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration. CONCLUSION: BK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.

Simultaneous determination of multiple androgens in mice organs with liquid chromatography tandem mass spectrometry.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide. It is essentially dependent on potent androgens, such as testosterone (T) and dihydrotestosterone (DHT). The precursors of T and DHT, which includes androstenedione (A4) and dihydroepiandrosterone (DHEA), and also the metabolites of DHT, 5α-androstane-3α,17ß-diol (3α-Diol) and 5α-androstane-3ß,17ß-diol (3ß-Diol) are able to affect the development of PCa. Therefore, it is important to simultaneously determine all these key androgens. This study aims to develop and validate an LC-MS/MS quantification method to simultaneously detect and quantify the six related androgens, including T, DHT, A4, DHEA, 3α-Diol, and 3ß-Diol in limited sample volume. The sample preparation involved liquid extraction with methyl tert-butyl ether (MTBE), following by chemical derivatisation with hydroxylamine. The limits of quantitation for T, DHT, A4, and DHEA were 0.05nM and 3α-Diol and 3ß-Diol were 0.5nM with S/N ratio of at least 5:1 by using 100µL samples.

Preparation and characterization of 4-isopropylcalix[4]arene-capped (3-(2-O-ß-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles as chiral stationary phase for high-performance liquid chromatography.

A new type of 4-isopropylcalix[4]arene-capped (3-(2-O-ß-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (IPC4CD-HPS) has been prepared by treatment of bromoacetate-substituted (3-(2-O-ß-cyclodextrin)-2-hydroxypropoxy)propylsilyl-appended silica particles (BACD-HPS) with 4-isopropylcalix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The bonded silica IPC4CD-HPS has been successfully used as chiral stationary phase (CSP) in high-performance liquid chromatography (HPLC) for the first time. The synthetic stationary phase was characterized by means of elemental analysis and Fourier transform infrared spectroscopy. This new CSP has a chiral selector with two anchored functional moieties: 4-isopropylcalix[4]arene and ß-cyclodextrin. The chromatographic performance of IPC4CD-HPS was investigated by separation of positional isomers of several disubstituted benzenes and enantiomers of some chiral drug compounds under reversed-phase conditions. The results showed that IPC4CD-HPS had excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of the anchored 4-isopropylcalix[4]arenes and ß-cyclodextrins.