Mass spectrometry-based identification of new serum biomarkers in patients with latent infection pulmonary tuberculosis.

Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are still desperately needed. The aim of this study was to screen and identify possible biomarkers for diagnosing LTBI and monitoring the progression from latent infection to active TB infection, as well as to investigate the underlying processes and functions. To assess changes in metabolite composition associated with active tuberculosis infection in humans, whole blood supernatants were collected from patients with LTBI, drug-susceptible TB patients, drug-resistant TB patients, and healthy controls. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then detected by liquid chromatography-tandem mass spectrometry/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, and 1-way analysis of variance analysis among groups showed that P-value < 0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. 65 metabolites were substantially different in four groups. Differential metabolites such as Inosine and Prostaglandin E1 may be important blood indicators for diagnosing mycobacterium tuberculosis latent infection, which were all tightly connected to amino acid metabolism, Biosynthesis of various secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. This study screened and identified Inosine, 16, 16-dimethyl-6-keto Prostaglandin E1, Theophylline, and Cotinine as potential serum biomarkers for diagnosing latent TB infection, and Cotinine as potential biomarkers for monitoring disease progression from healthy population to LTBI and then to active TB including drug-resistant TB infection and sensitive TB infection. Furthermore, this research provides a preliminary experimental basis to further investigate the development of metabolomics-based diagnosis of LTBI and monitoring the progress from latent infection to active TB infection.

Imaging Nuclei of MDA-MB-231 Breast Cancer Cells by Chiral Ruthenium(II) Complex Coordinated by 2-(4-Phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline.

A pair of chiral ruthenium(II) complexes, Λ- and Δ-[Ru(bpy)2(p-BEPIP)](ClO4)2 [Λ- and Δ-RM0627; bpy = 2,2-bipyridine; p-BEPIP = 2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline], were prepared using the Sonogashira coupling reaction under microwave irradiation. The study shows that Λ-RM0627 emitted strong phosphorescence in the range 500-700 nm with a maximum at 594 nm when excited at 365 nm (the Stokes shift is about 227 nm), which was mainly located in the cell nucleus with red phosphorescence. Further studies using real-time phosphorescence observation confirmed that Λ-RM0627 can be taken up quickly by MDA-MB-231 cells and enriched in the nucleus. The in vitro and in vivo toxicities of Λ-RM0627 were also evaluated, and it was found that Λ-RM0627 slightly inhibited the growth of MDA-MB-231 breast cancer cells and HaCaT normal human epidermal cells and had little influence on the development of Zebrafish embryos at low concentration. In conclusion, the levoisomer of chiral ruthenium complexes can act as a potential phosphorescent probe that targets nuclei of living cells with low toxicity.